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Assessing copy number aberrations and copy neutral loss of heterozygosity across the genome as best practice: An evidence based review of clinical utility from the cancer genomics consortium (CGC) working group for myelodysplastic syndrome, myelodysplastic/myeloproliferative and myeloproliferative neoplasms

      Highlights

      • Assessment of clinically significant copy number alterations (CNAs) and copy-neutral loss-of-heterozygosity (CN-LOH) in myeloid malignancies by chromosomal microarray (CMA) can improve diagnostic yield, refine risk-stratification and provide genomic information to guide therapy. The Cancer Genomics Consortium (CGC) Working Group for Myeloid Neoplasms performed an extensive systematic examination of the peer-reviewed literature to evaluate the clinical value of CMA in the workup of myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and myeloproliferative neoplasms (MPN). This evidence based review provides:
        • 1.
          Specific clinical scenarios where CMA complements other standard-of-care testing modalities
        • 2.
          An example of a testing algorithm incorporating CMA within the backbone of the current testing guidelines
        • 3.
          An exhaustive list of recurrent CNAs and CN-LOH observed in these myeloid neoplasms and their clinical significance.

      Abstract

      Multiple studies have demonstrated the utility of chromosomal microarray (CMA) testing to identify clinically significant copy number alterations (CNAs) and copy-neutral loss-of-heterozygosity (CN-LOH) in myeloid malignancies. However, guidelines for integrating CMA as a standard practice for diagnostic evaluation, assessment of prognosis and predicting treatment response are still lacking. CMA has not been recommended for clinical work-up of myeloid malignancies by the WHO 2016 or the NCCN 2017 guidelines but is a suggested test by the European LeukaemiaNet 2013 for the diagnosis of primary myelodysplastic syndrome (MDS). The Cancer Genomics Consortium (CGC) Working Group for Myeloid Neoplasms systematically reviewed peer-reviewed literature to determine the power of CMA in (1) improving diagnostic yield, (2) refining risk stratification, and (3) providing additional genomic information to guide therapy. In this manuscript, we summarize the evidence base for the clinical utility of array testing in the workup of MDS, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and myeloproliferative neoplasms (MPN). This review provides a list of recurrent CNAs and CN-LOH noted in this disease spectrum and describes the clinical significance of the aberrations and how they complement gene mutation findings by sequencing. Furthermore, for new or suspected diagnosis of MDS or MPN, we present suggestions for integrating genomic testing methods (CMA and mutation testing by next generation sequencing) into the current standard-of-care clinical laboratory testing (karyotype, FISH, morphology, and flow).

      Keywords

      List of acronyms:

      aCGH (array-based comparative genomic hybridization), CN-LOH (copy neutral loss of heterozygosity), MDS (myelodysplastic syndrome), MPN (myeloproliferative neoplasm), CMA (Chromosomal Microarray), CGAT (chromosome genomic array testing), RARS-T ((Refractory anemia with ring sideroblasts and thrombocytosis), SNP-A (single-nucleotide polymorphism array), NCCN (National Comprehensive Cancer Network), WHO (World Health Organization), NGS (Next Generation Sequencing), FISH (Fluorescence In Situ Hybridization)

      Introduction

      The integration of genetic data into the clinical and pathological assessment of myeloid neoplasms underscores the expanding role of genomic changes in the diagnosis, prognosis, classification and therapeutic implications of precision medicine. Myeloid neoplasms include myelodysplastic syndrome (MDS), myelodysplastic/ myeloproliferative neoplasm (MDS/MPN), myeloproliferative neoplasm (MPN) and acute myeloid leukemia (AML). The myelodysplastic syndromes (MDS) comprise a very heterogeneous group of clonal myeloid disorders characterized by peripheral blood cytopenias, a bone marrow aspirate/biopsy showing dysplasia in one or more hematopoietic lineages and/or the presence of characteristic chromosome abnormalities [
      • Arber DA
      • Orazi A
      • Hasserjian R
      • Thiele J
      • Borowitz MJ
      • Le Beau MM
      • et al.
      The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.
      ,
      • Schanz J
      • Tuchler H
      • Sole F
      • Mallo M
      • Luno E
      • Cervera J
      • et al.
      New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge.
      ]. In addition, karyotype is a critical component of the International Prognostic Scoring System (IPSS), the gold standard used to predict overall survival and risk of AML transformation in primary MDS patients [
      • Greenberg P
      • Cox C
      • LeBeau MM
      • Fenaux P
      • Morel P
      • Sanz G
      • et al.
      International scoring system for evaluating prognosis in myelodysplastic syndromes.
      ]. The recently revised IPSS or IPSS-R refined the cytogenetics categories listed in the original IPSS and provided “greater weight” to the cytogenetic categories, underscoring the importance of genetic-based testing in the myeloid malignancies [
      • Greenberg PL
      • Tuechler H
      • Schanz J
      • Sanz G
      • Garcia-Manero G
      • Sole F
      • et al.
      Revised international prognostic scoring system for myelodysplastic syndromes.
      ]. However, karyotype analysis only detects chromosome abnormalities in ∼ 50% of primary MDS patients. Thus, to further improve the genetic diagnostic and prognostic precision in MDS and identify therapeutic targets, molecular genetic assays such as CMAs and NGS are needed. MPNs are clonal hematopoietic disorders characterized by proliferation of one or more of the myeloid lineages, while MDS/MPNs have features of both MDS and MPN at the time of initial presentation [
      • Arber DA
      • Orazi A
      • Hasserjian R
      • Thiele J
      • Borowitz MJ
      • Le Beau MM
      • et al.
      The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.
      ]. Per current NCCN guidelines for MPN, the diagnosis of MPN is based on the 2016 WHO criteria and requires a combination of clinical, laboratory, cytogenetics, and molecular testing [
      • Arber DA
      • Orazi A
      • Hasserjian R
      • Thiele J
      • Borowitz MJ
      • Le Beau MM
      • et al.
      The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.
      ,
      • Mesa R
      • Jamieson C
      • Bhatia R
      • Deininger MW
      • Gerds AT
      • Gojo I
      • et al.
      Myeloproliferative Neoplasms, Version 2.2017, NCCN clinical practice guidelines in oncology.
      ,
      • Mesa RA
      • Jamieson C
      • Bhatia R
      • Deininger MW
      • Fletcher CD
      • Gerds AT
      • et al.
      NCCN guidelines insights: myeloproliferative neoplasms, Version 2.2018.
      ]. For chronic myeloid leukemia (CML), defined by the presence of BCR/ABL1 rearrangement, RT-PCR or FISH with or without conventional karyotype are recommended for diagnosis. For BCR/ABL1-negative MPNs, in the absence of mutations of JAK2, MPL and CALR, chromosomal abnormalities can represent markers of clonality. Similarly, diagnosis of certain subcategories of MDS/MPN such as chronic myelomonocytic leukemia is facilitated by detection of chromosomal abnormalities, especially in the absence of diagnostic morphologic features [
      • Arber DA
      • Orazi A
      • Hasserjian R
      • Thiele J
      • Borowitz MJ
      • Le Beau MM
      • et al.
      The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.
      ].
      Numerous studies described below have demonstrated the utility of chromosomal microarray (CMA) testing to identify copy number alterations (CNAs) and copy neutral loss of heterozygosity (CN-LOH) in myeloid malignancies for diagnostic evaluation and assessment of prognosis; certain CN-LOH have significant therapeutic implications due to underlying mutations that could be potential therapeutic targets or predict treatment response. However, CMA, also known as array comparative genome hybridization (aCGH), single nucleotide polymorphism array (SNP-A), chromosome genomic array testing (CGAT), DNA microarray testing, genomic array or simply referred to as array, is still not a standard of practice across all cancer care institutions. Assessment of genomic aberrations by CMA testing has not been addressed by the WHO 2016 or the NCCN guidelines for clinical work-up of hematological malignancies [
      • Arber DA
      • Orazi A
      • Hasserjian R
      • Thiele J
      • Borowitz MJ
      • Le Beau MM
      • et al.
      The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.
      ,
      • Greenberg PL
      • Stone RM
      • Al-Kali A
      • Barta SK
      • Bejar R
      • Bennett JM
      • et al.
      Myelodysplastic syndromes, Version 2.2017, NCCN clinical practice guidelines in oncology.
      ,
      • Mesa RA
      The new NCCN guidelines for the management of myelofibrosis.
      ]; European LeukaemiaNet 2013 has suggested the use of CMA testing for the diagnosis of primary MDS [
      • Malcovati L
      • Hellstrom-Lindberg E
      • Bowen D
      • Ades L
      • Cermak J
      • Del Canizo C
      • et al.
      Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet.
      ]. However, at this time, there are no specific guidelines available for clinical utilization (i.e., when and how to perform CMA analysis).
      To evaluate the clinical utility of CMA in hematological malignancies, the Cancer Genomics Consortium (CGC) Working Group for Myeloid Neoplasms was formed comprising cytogenetics, molecular genetics, and pathology experts under the auspices of the CGC. An extensive systematic examination of the peer-reviewed literature was performed to evaluate the clinical value of CMA and to identify the recurrent CNAs and CN-LOH in various myeloid malignancies. According to the 2016 WHO classification, diseases reviewed in this manuscript include MDS, MDS/MPN, and MPN including CML. For each recurrent CNA (gain or loss) or CN-LOH, the clinical significance of the affected gene(s) in various myeloid disorders and their corresponding impact on clinical management were assessed.
      Here, we present the evidence base for the clinical utility of array testing in myeloid neoplasms (MDS, MDS/MPN and MPN), and provide suggestions for clinical utilization and methodology considerations.

      Materials and methods

      Literature search and review

      A literature search was performed for articles on PubMed using a combination of the following terminologies: “MDS; MPN; MDS/MPN; chronic myelomonocytic leukemia (CMML) and myeloid neoplasms” with “microarray; SNP array; array CGH; loss of heterozygosity/LOH; uniparental disomy/UPD; copy number. A total of 66 peer-reviewed articles were reviewed in-depth up to 2017. These studies utilized one of the three common microarray platforms, namely, Agilent copy number (CN) or CN + SNP arrays, Affymetrix CN + SNP arrays, or Illumina-SNP arrays. The following data from each of the articles were collected: type of study, array platform, total number of cases in the study, disease type and WHO sub-classification whenever available; time point of testing during the disease course, criteria for making the calls (gains/ losses/ CN-LOH), diagnostic yield, recurrent CNA and CN-LOH findings and their clinical significance (diagnostic/ prognostic/ therapeutic targets) and their role in clonal evolution and disease transformation from MDS or MPN to AML. The primary literature was also evaluated to identify the spectrum of recurrently affected genomic regions and genes, regardless of known clinical significance, in MDS, MDS/MPN or MPN as ascertained through chromosomal microarray analysis.  Review articles and articles related to primary or secondary AML cases were excluded.
      Recurrent CNA and CN-LOH detected across the myeloid neoplasms were retrieved. Clinical significance was based on the utility for (a) diagnosis; (b) prognostication; (c) predictive marker for therapeutics (targeted agents or precision medicine); and/or d) correlation of other clinical-pathological findings of interest, e.g., morphologic subtypes, flow cytometry immunophenotype, association with somatic mutations, microRNAs, etc. Because variable criteria for aberrant CNA and CN-LOH calls were used in the literature, we applied the following consistent inclusion criteria for the purpose of this review to obtain comparable data across all articles: included CNAs generally ≥100 Kb in size and CN-LOH regions of ≥10 Mb and telomeric for CN-LOH regions that occurred in ≥ 2 patients in a single study unless of known clinical significance or proven somatic by paired germline tissue array analysis. For each recurrent CNA and CN-LOH, gene content (if known), disease type and clinical significance were recorded.
      The level of evidence for clinical significance of CNAs was assigned as follows: Level 1, well established: present in current WHO classification (adapted from IPSS [
      • Greenberg P
      • Cox C
      • LeBeau MM
      • Fenaux P
      • Morel P
      • Sanz G
      • et al.
      International scoring system for evaluating prognosis in myelodysplastic syndromes.
      ]/IPSS-R [
      • Greenberg PL
      • Tuechler H
      • Schanz J
      • Sanz G
      • Garcia-Manero G
      • Sole F
      • et al.
      Revised international prognostic scoring system for myelodysplastic syndromes.
      ] for MDS) [
      • Arber DA
      • Orazi A
      • Hasserjian R
      • Thiele J
      • Borowitz MJ
      • Le Beau MM
      • et al.
      The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.
      ,
      • Schanz J
      • Tuchler H
      • Sole F
      • Mallo M
      • Luno E
      • Cervera J
      • et al.
      New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge.
      ,
      • Greenberg PL
      • Tuechler H
      • Schanz J
      • Sanz G
      • Garcia-Manero G
      • Sole F
      • et al.
      Revised international prognostic scoring system for myelodysplastic syndromes.
      ] and/or professional practice guidelines (NCCN for MDS [
      • Greenberg PL
      • Stone RM
      • Al-Kali A
      • Barta SK
      • Bejar R
      • Bennett JM
      • et al.
      Myelodysplastic syndromes, Version 2.2017, NCCN clinical practice guidelines in oncology.
      ] and MPN [
      • Mesa R
      • Jamieson C
      • Bhatia R
      • Deininger MW
      • Gerds AT
      • Gojo I
      • et al.
      Myeloproliferative Neoplasms, Version 2.2017, NCCN clinical practice guidelines in oncology.
      ] and International MDS/MPN Working Group's recommendations for MDS/MPN [
      • Mughal TI
      • Cross NC
      • Padron E
      • Tiu RV
      • Savona M
      • Malcovati L
      • et al.
      An international MDS/MPN working group's perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms.
      ]; Level 2, emerging: defined here as recurrent (≥5 cases) in well-powered studies with expert consensus; and Level 3, other recurrent abnormalities present in either ≥ 5 cases that do not meet levels 1 or 2 or in ≥ 2 cases of deletion that overlaps a myeloid-associated gene with previously described loss-of-function mutations. The level of evidence for clinical significance of CN-LOH was assigned as follows: Level 1, well established, present in current WHO classification and/or professional practice guidelines; Level 2, emerging, defined here as present in ≥ 2 cases, including a known myeloid gene from NCCN guidelines (22 genes), ≥ 10 MB, and at least one study proved the affected region is not germline; and Level 3, other recurrent abnormalities present in ≥ 2 cases that do not meet levels 1 or 2 and includes at least one known myeloid gene from a non-NCCN guidelines source (99 genes) and ≥ 10 MB [
      • Papaemmanuil E
      • Gerstung M
      • Malcovati L
      • Tauro S
      • Gundem G
      • Van Loo P
      • et al.
      Clinical and biological implications of driver mutations in myelodysplastic syndromes.
      ].

      Results

      The results of this analysis are organized into different sub-headings for the sake of clarity:
      • I.
        Evidence of improved diagnostic yield by CMA in myeloid neoplasms
        • a.
          Detection of CNAs
        • b.
          Detection of CN-LOH
        • c.
          Utility in cases with non-informative karyotype
      • II.
        Summary of the disease-based prognostic and therapeutic implications of CMA findings:
        • a.
          Myeloid disorders classified per 2016 WHO classification: MDS, MDS/MPN and MPN(CML and BCR/ABL1 negative MPNs)
        • b.
          Myeloid disorders with specific genetic abnormalities: del(5q), TET2 alterations, TP53 mutations, Trisomy 8 and del(20q)
        • c.
          Bone marrow failure syndrome (BMFS)
        • d.
          Precursor myeloid entities: idiopathic cytopenias of undetermined significance (ICUS), idiopathic dysplasia of undetermined significance (IDUS), clonal cytopenias of undetermined significance (CCUS) and clonal hematopoiesis of indeterminate potential (CHIP)
      • III.
        Important Pre-analytical and Post-analytical considerations for CMA and limitations of CMA testing
        • a.
          Peripheral Blood vs. Bone Marrow
        • b.
          Formalin fixed paraffin embedded (FFPE) material
      • IV.
        Limitations of CMA

      CMA facilitates improved diagnostic yield in myeloid neoplasms

      Detection of CNAs

      The overall detection rate by CMA in all myeloid neoplasms ranged between 19 and 83%. In patients with normal karyotype, the detection rate ranged between 33% and 62% [
      • Gondek LP
      • Tiu R
      • O'Keefe CL
      • Sekeres MA
      • Theil KS
      • Maciejewski JP
      Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML.
      ]. In patients with both normal karyotype and normal FISH, CMA detection rate was 25% whereas in patients with normal FISH, karyotype and NGS studies, the detection rate was 10% (6 of 59) of patients in a large study [
      • Mukherjee S
      • Sathanoori M
      • Ma Z
      • Andreatta M
      • Lennon PA
      • Wheeler SR
      • et al.
      Addition of chromosomal microarray and next generation sequencing to FISH and classical cytogenetics enhances genomic profiling of myeloid malignancies.
      ]. The higher detection rate of CMA is due to its ability to detect sub-microscopic CNAs beyond the resolution of karyotype and FISH. In addition, CNAs detected by CMA are potentially targetable by on-label and off-label FDA approved therapies in 46% of patients with myeloid malignancies [
      • Mukherjee S
      • Sathanoori M
      • Ma Z
      • Andreatta M
      • Lennon PA
      • Wheeler SR
      • et al.
      Addition of chromosomal microarray and next generation sequencing to FISH and classical cytogenetics enhances genomic profiling of myeloid malignancies.
      ]. The results are summarized in Table 1. Recurrent CNAs include gain of chromosomes 1p, 8, 9p, 13 and deletions of 4q, 5q, 7q, 11q, 12p, 17p, 20q, 21q, among others (see Table 24 for the complete list).
      Table 1Evidence for the clinical utility of chromosomal microarray testing (CMA) in myeloid disorders excluding acute myeloid leukemia.
      DiseaseOverall CMAKey and uniqueAlteredImpactReferences
      detection rateCMA aberrationsgene(s)
      MDS28–83% (Normal karyotype only: 11–39%)Total genomic alterationPrognostic poor survival
      • Starczynowski DT
      • Vercauteren S
      • Telenius A
      • Sung S
      • Tohyama K
      • Brooks-Wilson A
      • et al.
      High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival.
      ,
      • Yeung CCS
      • McElhone S
      • Chen XY
      • Ng D
      • Storer BE
      • Deeg HJ
      • et al.
      Impact of copy neutral loss of heterozygosity and total genome aberrations on survival in myelodysplastic syndrome.
      ,
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      ,
      • Cluzeau T
      • Moreilhon C
      • Mounier N
      • Karsenti JM
      • Gastaud L
      • Garnier G
      • et al.
      Total genomic alteration as measured by SNP-array-based molecular karyotyping is predictive of overall survival in a cohort of MDS or AML patients treated with azacitidine.
      ,
      • Ganster C
      • Shirneshan K
      • Salinas-Riester G
      • Braulke F
      • Schanz J
      • Platzbecker U
      • et al.
      Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS.
      1p CN-LOHPrognostic for progression to AML
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Gondek LP
      • Haddad AS
      • O'Keefe CL
      • Tiu R
      • Wlodarski MW
      • Sekeres MA
      • et al.
      Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Sugimoto Y
      • Sekeres MA
      • Makishima H
      • Traina F
      • Visconte V
      • Jankowska A
      • et al.
      Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      1q gainRecurrent
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      4q lossTET2Prognostic for poor survival
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Jankowska AM
      • Szpurka H
      • Tiu RV
      • Makishima H
      • Afable M
      • Huh J
      • et al.
      Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms.
      ,
      • Bacher U
      • Weissmann S
      • Kohlmann A
      • Schindela S
      • Alpermann T
      • Schnittger S
      • et al.
      TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele.
      ,
      • Kolquist KA
      • Schultz RA
      • Furrow A
      • Brown TC
      • Han JY
      • Campbell LJ
      • et al.
      Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
      4q CN-LOHTET2Prognostic for poor survival
      • Gondek LP
      • Tiu R
      • O'Keefe CL
      • Sekeres MA
      • Theil KS
      • Maciejewski JP
      Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML.
      ,
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Heinrichs S
      • Kulkarni RV
      • Bueso-Ramos CE
      • Levine RL
      • Loh ML
      • Li C
      • et al.
      Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Mohamedali AM
      • Smith AE
      • Gaken J
      • Lea NC
      • Mian SA
      • Westwood NB
      • et al.
      Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome.
      ,
      • Mohamedali A
      • Gaken J
      • Twine NA
      • Ingram W
      • Westwood N
      • Lea NC
      • et al.
      Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      ,
      • Larsson N
      • Lilljebjorn H
      • Lassen C
      • Johansson B
      • Fioretos T
      Myeloid malignancies with acquired trisomy 21 as the sole cytogenetic change are clinically highly variable and display a heterogeneous pattern of copy number alterations and mutations.
      5q loss5q loss “size” prognostic for progression to AML
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Huh J
      • Jung CW
      • Kim HJ
      • Kim YK
      • Moon JH
      • Sohn SK
      • et al.
      Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Starczynowski DT
      • Vercauteren S
      • Telenius A
      • Sung S
      • Tohyama K
      • Brooks-Wilson A
      • et al.
      High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival.
      ,
      • Jerez A
      • Gondek LP
      • Jankowska AM
      • Makishima H
      • Przychodzen B
      • Tiu RV
      • et al.
      Topography, clinical, and genomic correlates of 5q myeloid malignancies revisited.
      ,
      • Stengel A
      • Kern W
      • Haferlach T
      • Meggendorfer M
      • Haferlach C
      The 5q deletion size in myeloid malignancies is correlated to additional chromosomal aberrations and to TP53 mutations.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      ,
      • Kunze K
      • Gamerdinger U
      • Lessig-Owlanj J
      • Sorokina M
      • Brobeil A
      • Tur MK
      • et al.
      Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis.
      7q lossCUX1, EZH2Prognostic for poor survival
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Huh J
      • Jung CW
      • Kim HJ
      • Kim YK
      • Moon JH
      • Sohn SK
      • et al.
      Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category.
      ,
      • Thiel A
      • Beier M
      • Ingenhag D
      • Servan K
      • Hein M
      • Moeller V
      • et al.
      Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Volkert S
      • Haferlach T
      • Holzwarth J
      • Zenger M
      • Kern W
      • Staller M
      • et al.
      Array CGH identifies copy number changes in 11% of 520 MDS patients with normal karyotype and uncovers prognostically relevant deletions.
      ,
      • Svobodova K
      • Zemanova Z
      • Lhotska H
      • Novakova M
      • Podskalska L
      • Belickova M
      • et al.
      Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.
      ,
      • Mohamedali A
      • Gaken J
      • Twine NA
      • Ingram W
      • Westwood N
      • Lea NC
      • et al.
      Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes.
      ,
      • Sugimoto Y
      • Sekeres MA
      • Makishima H
      • Traina F
      • Visconte V
      • Jankowska A
      • et al.
      Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      ,
      • Babushok DV
      • Xie HM
      • Roth JJ
      • Perdigones N
      • Olson TS
      • Cockroft JD
      • et al.
      Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes.
      ,
      • Stevens-Kroef MJ
      • Hebeda KM
      • Verwiel ET
      • Kamping EJ
      • van Cleef PH
      • Kuiper RP
      • et al.
      Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      ,
      • Barresi V
      • Palumbo GA
      • Musso N
      • Consoli C
      • Capizzi C
      • Meli CR
      • et al.
      Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML.
      ,
      • Kunze K
      • Gamerdinger U
      • Lessig-Owlanj J
      • Sorokina M
      • Brobeil A
      • Tur MK
      • et al.
      Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis.
      7q CN-LOHRecurrent
      • Gondek LP
      • Tiu R
      • O'Keefe CL
      • Sekeres MA
      • Theil KS
      • Maciejewski JP
      Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML.
      ,
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Gondek LP
      • Haddad AS
      • O'Keefe CL
      • Tiu R
      • Wlodarski MW
      • Sekeres MA
      • et al.
      Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Ganster C
      • Shirneshan K
      • Salinas-Riester G
      • Braulke F
      • Schanz J
      • Platzbecker U
      • et al.
      Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS.
      ,
      • Nowak D
      • Nolte F
      • Mossner M
      • Nowak V
      • Baldus CD
      • Hopfer O
      • et al.
      Genome-wide DNA-mapping of CD34+ cells from patients with myelodysplastic syndrome using 500 K SNP arrays identifies significant regions of deletion and uniparental disomy.
      ,
      • Larsson N
      • Lilljebjorn H
      • Lassen C
      • Johansson B
      • Fioretos T
      Myeloid malignancies with acquired trisomy 21 as the sole cytogenetic change are clinically highly variable and display a heterogeneous pattern of copy number alterations and mutations.
      11q CN-LOHCBLPrognostic/ recurrent
      • Gondek LP
      • Tiu R
      • O'Keefe CL
      • Sekeres MA
      • Theil KS
      • Maciejewski JP
      Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML.
      ,
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Huh J
      • Jung CW
      • Kim HJ
      • Kim YK
      • Moon JH
      • Sohn SK
      • et al.
      Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category.
      ,
      • Gondek LP
      • Haddad AS
      • O'Keefe CL
      • Tiu R
      • Wlodarski MW
      • Sekeres MA
      • et al.
      Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes.
      ,
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      12p lossETV6Recurrent
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Heinrichs S
      • Kulkarni RV
      • Bueso-Ramos CE
      • Levine RL
      • Loh ML
      • Li C
      • et al.
      Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Volkert S
      • Haferlach T
      • Holzwarth J
      • Zenger M
      • Kern W
      • Staller M
      • et al.
      Array CGH identifies copy number changes in 11% of 520 MDS patients with normal karyotype and uncovers prognostically relevant deletions.
      ,
      • Kolquist KA
      • Schultz RA
      • Furrow A
      • Brown TC
      • Han JY
      • Campbell LJ
      • et al.
      Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
      13q loss?RB1Recurrent
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Volkert S
      • Haferlach T
      • Holzwarth J
      • Zenger M
      • Kern W
      • Staller M
      • et al.
      Array CGH identifies copy number changes in 11% of 520 MDS patients with normal karyotype and uncovers prognostically relevant deletions.
      ,
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      17p lossTP53Recurrent
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Zhang R
      • Kim YM
      • Wang X
      • Li Y
      • Lu X
      • Sternenberger AR
      • et al.
      Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and/or -7/del(7q).
      ,
      • Kolquist KA
      • Schultz RA
      • Furrow A
      • Brown TC
      • Han JY
      • Campbell LJ
      • et al.
      Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
      ,
      • Stevens-Kroef MJ
      • Hebeda KM
      • Verwiel ET
      • Kamping EJ
      • van Cleef PH
      • Kuiper RP
      • et al.
      Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome.
      17p CN-LOHTP53Diagnostic for advanced MDS/sAML
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Svobodova K
      • Zemanova Z
      • Lhotska H
      • Novakova M
      • Podskalska L
      • Belickova M
      • et al.
      Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.
      20q lossRecurrent
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Sugimoto Y
      • Sekeres MA
      • Makishima H
      • Traina F
      • Visconte V
      • Jankowska A
      • et al.
      Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
      ,
      • Vercauteren SM
      • Sung S
      • Starczynowski DT
      • Lam WL
      • Bruyere H
      • Horsman DE
      • et al.
      Array comparative genomic hybridization of peripheral blood granulocytes of patients with myelodysplastic syndrome detects karyotypic abnormalities.
      ,
      • da Silva FB
      • Machado-Neto JA
      • Bertini V
      • Velloso E
      • Ratis CA
      • Calado RT
      • et al.
      Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome.
      ,
      • Stevens-Kroef MJ
      • Hebeda KM
      • Verwiel ET
      • Kamping EJ
      • van Cleef PH
      • Kuiper RP
      • et al.
      Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome.
      ,
      • Barresi V
      • Palumbo GA
      • Musso N
      • Consoli C
      • Capizzi C
      • Meli CR
      • et al.
      Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML.
      ,
      • Kunze K
      • Gamerdinger U
      • Lessig-Owlanj J
      • Sorokina M
      • Brobeil A
      • Tur MK
      • et al.
      Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis.
      21q CN-LOH or deletionRUNX1Prognostic for progression to AML
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Thiel A
      • Beier M
      • Ingenhag D
      • Servan K
      • Hein M
      • Moeller V
      • et al.
      Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance.
      ,
      • Volkert S
      • Haferlach T
      • Holzwarth J
      • Zenger M
      • Kern W
      • Staller M
      • et al.
      Array CGH identifies copy number changes in 11% of 520 MDS patients with normal karyotype and uncovers prognostically relevant deletions.
      ,
      • Kolquist KA
      • Schultz RA
      • Furrow A
      • Brown TC
      • Han JY
      • Campbell LJ
      • et al.
      Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
      ,
      • Sugimoto Y
      • Sekeres MA
      • Makishima H
      • Traina F
      • Visconte V
      • Jankowska A
      • et al.
      Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
      ,
      • Nowak D
      • Nolte F
      • Mossner M
      • Nowak V
      • Baldus CD
      • Hopfer O
      • et al.
      Genome-wide DNA-mapping of CD34+ cells from patients with myelodysplastic syndrome using 500 K SNP arrays identifies significant regions of deletion and uniparental disomy.
      MDS/MPN73%/NA4q CN-LOHTET2Recurrent
      • Gondek LP
      • Tiu R
      • O'Keefe CL
      • Sekeres MA
      • Theil KS
      • Maciejewski JP
      Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML.
      ,
      • Palomo L
      • Xicoy B
      • Garcia O
      • Mallo M
      • Adema V
      • Cabezon M
      • et al.
      Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases.
      ,
      • Jankowska AM
      • Szpurka H
      • Tiu RV
      • Makishima H
      • Afable M
      • Huh J
      • et al.
      Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      ,
      • da Silva FB
      • Machado-Neto JA
      • Bertini V
      • Velloso E
      • Ratis CA
      • Calado RT
      • et al.
      Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome.
      7q CN-LOHLikely CUX1Recurrent
      • Gondek LP
      • Tiu R
      • O'Keefe CL
      • Sekeres MA
      • Theil KS
      • Maciejewski JP
      Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML.
      ,
      • Palomo L
      • Xicoy B
      • Garcia O
      • Mallo M
      • Adema V
      • Cabezon M
      • et al.
      Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Sugimoto Y
      • Sekeres MA
      • Makishima H
      • Traina F
      • Visconte V
      • Jankowska A
      • et al.
      Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      11q CN-LOHCBLRecurrent
      • Gondek LP
      • Tiu R
      • O'Keefe CL
      • Sekeres MA
      • Theil KS
      • Maciejewski JP
      Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML.
      ,
      • Palomo L
      • Xicoy B
      • Garcia O
      • Mallo M
      • Adema V
      • Cabezon M
      • et al.
      Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases.
      ,
      • Jankowska AM
      • Szpurka H
      • Tiu RV
      • Makishima H
      • Afable M
      • Huh J
      • et al.
      Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Gondek LP
      • Dunbar AJ
      • Szpurka H
      • McDevitt MA
      • Maciejewski JP
      SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD.
      MPN>56%/NA1q gainRecurrent
      • Rumi E
      • Harutyunyan A
      • Elena C
      • Pietra D
      • Klampfl T
      • Bagienski K
      • et al.
      Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm.
      ,
      • Singh NR
      • Morris CM
      • Koleth M
      • Wong K
      • Ward CM
      • Stevenson WS
      Polyploidy in myelofibrosis: analysis by cytogenetic and SNP array indicates association with advancing disease.
      ,
      • Hahm C
      • Huh HJ
      • Mun YC
      • Seong CM
      • Chung WS
      • Huh J
      Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression.
      4q lossTET2Prognostic for progression to AML
      • Bacher U
      • Weissmann S
      • Kohlmann A
      • Schindela S
      • Alpermann T
      • Schnittger S
      • et al.
      TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele.
      ,
      • Klampfl T
      • Harutyunyan A
      • Berg T
      • Gisslinger B
      • Schalling M
      • Bagienski K
      • et al.
      Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression.
      9p CN-LOHJAK2Predictive for JAK2 inhibitors; Prognostic for PV progression to MF
      • Rumi E
      • Harutyunyan A
      • Elena C
      • Pietra D
      • Klampfl T
      • Bagienski K
      • et al.
      Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm.
      ,
      • Gondek LP
      • Dunbar AJ
      • Szpurka H
      • McDevitt MA
      • Maciejewski JP
      SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD.
      ,
      • Singh NR
      • Morris CM
      • Koleth M
      • Wong K
      • Ward CM
      • Stevenson WS
      Polyploidy in myelofibrosis: analysis by cytogenetic and SNP array indicates association with advancing disease.
      ,
      • Hahm C
      • Huh HJ
      • Mun YC
      • Seong CM
      • Chung WS
      • Huh J
      Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression.
      ,
      • Stegelmann F
      • Bullinger L
      • Griesshammer M
      • Holzmann K
      • Habdank M
      • Kuhn S
      • et al.
      High-resolution single-nucleotide polymorphism array-profiling in myeloproliferative neoplasms identifies novel genomic aberrations.
      14q CN-LOHPresence of CNAs/CN-LOH prognostic for progression to AML
      • Rumi E
      • Harutyunyan A
      • Elena C
      • Pietra D
      • Klampfl T
      • Bagienski K
      • et al.
      Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm.
      ,
      • Singh NR
      • Morris CM
      • Koleth M
      • Wong K
      • Ward CM
      • Stevenson WS
      Polyploidy in myelofibrosis: analysis by cytogenetic and SNP array indicates association with advancing disease.
      ,
      • Hahm C
      • Huh HJ
      • Mun YC
      • Seong CM
      • Chung WS
      • Huh J
      Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression.
      ,
      • Sugimoto Y
      • Sekeres MA
      • Makishima H
      • Traina F
      • Visconte V
      • Jankowska A
      • et al.
      Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
      20q lossRecurrent
      • Rumi E
      • Harutyunyan A
      • Elena C
      • Pietra D
      • Klampfl T
      • Bagienski K
      • et al.
      Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm.
      ,
      • Singh NR
      • Morris CM
      • Koleth M
      • Wong K
      • Ward CM
      • Stevenson WS
      Polyploidy in myelofibrosis: analysis by cytogenetic and SNP array indicates association with advancing disease.
      ,
      • Huh J
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Jasek M
      • Makishima H
      • et al.
      Characterization of chromosome arm 20q abnormalities in myeloid malignancies using genome-wide single nucleotide polymorphism array analysis.
      CML21–24%/NA17p lossTP53Recurrent, progression, associated with TKI resistance
      • Nowak D
      • Ogawa S
      • Muschen M
      • Kato M
      • Kawamata N
      • Meixel A
      • et al.
      SNP array analysis of tyrosine kinase inhibitor-resistant chronic myeloid leukemia identifies heterogeneous secondary genomic alterations.
      ,
      • Boultwood J
      • Perry J
      • Zaman R
      • Fernandez-Santamaria C
      • Littlewood T
      • Kusec R
      • et al.
      High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression.
      2q CN-LOHDiagnostic (only seen in BC)
      • Boultwood J
      • Perry J
      • Zaman R
      • Fernandez-Santamaria C
      • Littlewood T
      • Kusec R
      • et al.
      High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression.
      8p CN-LOHDiagnostic (only seen in BC)
      • Boultwood J
      • Perry J
      • Zaman R
      • Fernandez-Santamaria C
      • Littlewood T
      • Kusec R
      • et al.
      High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression.
      BMFS19% (AA)6p CN-LOH?HLA genesRecurrent
      • Afable MG
      • Wlodarski M
      • Makishima H
      • Shaik M
      • Sekeres MA
      • Tiu RV
      • et al.
      SNP array-based karyotyping: differences and similarities between aplastic anemia and hypocellular myelodysplastic syndromes.
      ,
      • Babushok DV
      • Xie HM
      • Roth JJ
      • Perdigones N
      • Olson TS
      • Cockroft JD
      • et al.
      Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes.
      ,
      • Betensky M
      • Babushok D
      • Roth JJ
      • Mason PJ
      • Biegel JA
      • Busse TM
      • et al.
      Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia.
      AA, Aplastic anemia; BMFS, Bone Marrow Failure Syndrome; MDS, Myelodysplastic Syndrome; MDS/MPN, Myelodysplastic/ myeloproliferative Neoplasm; MPN, Myeloproliferative Neoplasm; CML, Chronic Myelogeneous Leukemia; sAML, secondary AML; TGA, Total genomic aberration; TKI, tyrosine kinase inhibitors.
      *Recurrent indicates recurrent aberration with no established prognostic significance.
      Table 2A comprehensive list of CNAs and CN-LOH of known or likely clinical significance in MDS detected by CMA testing.
      ChromosomeDiseaseAbnormality TypeRegionRelevant GenesClinicalLevel ofReferences
      (Gain, Loss, CN-LOH)(if known)Significance
      Clinical significance based on WHO classification using IPSS-R (Greenberg et al., Blood 2012; Schanz et al., J Clin Oncol 2011).
      Evidence
      1MDSGain1p36.33-p33MPLRecurrent3
      • Huh J
      • Jung CW
      • Kim HJ
      • Kim YK
      • Moon JH
      • Sohn SK
      • et al.
      Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category.


      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Vercauteren SM
      • Sung S
      • Starczynowski DT
      • Lam WL
      • Bruyere H
      • Horsman DE
      • et al.
      Array comparative genomic hybridization of peripheral blood granulocytes of patients with myelodysplastic syndrome detects karyotypic abnormalities.
      1MDSCN-LOH1pMPLRecurrent2
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Gondek LP
      • Haddad AS
      • O'Keefe CL
      • Tiu R
      • Wlodarski MW
      • Sekeres MA
      • et al.
      Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Sugimoto Y
      • Sekeres MA
      • Makishima H
      • Traina F
      • Visconte V
      • Jankowska A
      • et al.
      Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
      1MDSGain1qRecurrent2
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      2MDSCN-LOH2pter-2p13.3DNMT3ARecurrent2
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Stengel A
      • Kern W
      • Haferlach T
      • Meggendorfer M
      • Haferlach C
      The 5q deletion size in myeloid malignancies is correlated to additional chromosomal aberrations and to TP53 mutations.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      ,
      • Hahm C
      • Mun YC
      • Seong CM
      • Han SH
      • Chung WS
      • Huh J
      Single nucleotide polymorphism array-based karyotyping in acute myeloid leukemia or myelodysplastic syndrome with trisomy 8 as the sole chromosomal abnormality.
      3MDSCN-LOH3q21.3-qterMECOM, GATA2Recurrent3
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Heinrichs S
      • Kulkarni RV
      • Bueso-Ramos CE
      • Levine RL
      • Loh ML
      • Li C
      • et al.
      Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.
      ,
      • Merkerova MD
      • Bystricka D
      • Belickova M
      • Krejcik Z
      • Zemanova Z
      • Polak J
      • et al.
      From cryptic chromosomal lesions to pathologically relevant genes: integration of SNP-array with gene expression profiling in myelodysplastic syndrome with normal karyotype.
      ,
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      ,
      • Sugimoto Y
      • Sekeres MA
      • Makishima H
      • Traina F
      • Visconte V
      • Jankowska A
      • et al.
      Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
      4MDSLoss4q24TET2T
      Potential marker for responsiveness to hypomethylating agents or DNA methyltransferase inhibitors (Bejar et al., Blood 124:2705–12, 2014;Traina et al., Leukemia 28:78–87, 2014).
      2
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Thiel A
      • Beier M
      • Ingenhag D
      • Servan K
      • Hein M
      • Moeller V
      • et al.
      Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Jankowska AM
      • Szpurka H
      • Tiu RV
      • Makishima H
      • Afable M
      • Huh J
      • et al.
      Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms.
      ,
      • Bacher U
      • Weissmann S
      • Kohlmann A
      • Schindela S
      • Alpermann T
      • Schnittger S
      • et al.
      TET2 deletions are a recurrent but rare phenomenon in myeloid malignancies and are frequently accompanied by TET2 mutations on the remaining allele.
      ,
      • Volkert S
      • Haferlach T
      • Holzwarth J
      • Zenger M
      • Kern W
      • Staller M
      • et al.
      Array CGH identifies copy number changes in 11% of 520 MDS patients with normal karyotype and uncovers prognostically relevant deletions.
      ,
      • Kolquist KA
      • Schultz RA
      • Furrow A
      • Brown TC
      • Han JY
      • Campbell LJ
      • et al.
      Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
      4MDSCN-LOH4q12-qterTET2Recurrent2
      • Gondek LP
      • Tiu R
      • O'Keefe CL
      • Sekeres MA
      • Theil KS
      • Maciejewski JP
      Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML.
      ,
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Heinrichs S
      • Kulkarni RV
      • Bueso-Ramos CE
      • Levine RL
      • Loh ML
      • Li C
      • et al.
      Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Mohamedali AM
      • Gaken J
      • Ahmed M
      • Malik F
      • Smith AE
      • Best S
      • et al.
      High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS).
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Mohamedali AM
      • Smith AE
      • Gaken J
      • Lea NC
      • Mian SA
      • Westwood NB
      • et al.
      Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome.
      ,
      • Mohamedali A
      • Gaken J
      • Twine NA
      • Ingram W
      • Westwood N
      • Lea NC
      • et al.
      Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      ,
      • Larsson N
      • Lilljebjorn H
      • Lassen C
      • Johansson B
      • Fioretos T
      Myeloid malignancies with acquired trisomy 21 as the sole cytogenetic change are clinically highly variable and display a heterogeneous pattern of copy number alterations and mutations.
      5MDSGain5pSuggestive of i(5p) with 5q delRecurrent3
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      5MDSLoss5qRPS14D, P (Good when isolated)1
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Huh J
      • Jung CW
      • Kim HJ
      • Kim YK
      • Moon JH
      • Sohn SK
      • et al.
      Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category.
      ,
      • Heinrichs S
      • Kulkarni RV
      • Bueso-Ramos CE
      • Levine RL
      • Loh ML
      • Li C
      • et al.
      Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.
      ,
      • Thiel A
      • Beier M
      • Ingenhag D
      • Servan K
      • Hein M
      • Moeller V
      • et al.
      Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance.
      ,
      • Merkerova MD
      • Bystricka D
      • Belickova M
      • Krejcik Z
      • Zemanova Z
      • Polak J
      • et al.
      From cryptic chromosomal lesions to pathologically relevant genes: integration of SNP-array with gene expression profiling in myelodysplastic syndrome with normal karyotype.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Starczynowski DT
      • Vercauteren S
      • Telenius A
      • Sung S
      • Tohyama K
      • Brooks-Wilson A
      • et al.
      High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Jerez A
      • Gondek LP
      • Jankowska AM
      • Makishima H
      • Przychodzen B
      • Tiu RV
      • et al.
      Topography, clinical, and genomic correlates of 5q myeloid malignancies revisited.
      ,
      • Zhang R
      • Kim YM
      • Wang X
      • Li Y
      • Lu X
      • Sternenberger AR
      • et al.
      Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and/or -7/del(7q).
      ,
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      ,
      • Svobodova K
      • Zemanova Z
      • Lhotska H
      • Novakova M
      • Podskalska L
      • Belickova M
      • et al.
      Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.
      ,
      • Bajaj R
      • Xu F
      • Xiang B
      • Wilcox K
      • Diadamo AJ
      • Kumar R
      • et al.
      Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia.
      ,
      • Mohamedali A
      • Gaken J
      • Twine NA
      • Ingram W
      • Westwood N
      • Lea NC
      • et al.
      Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes.
      ,
      • Ganster C
      • Shirneshan K
      • Salinas-Riester G
      • Braulke F
      • Schanz J
      • Platzbecker U
      • et al.
      Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS.
      ,
      • Vercauteren SM
      • Sung S
      • Starczynowski DT
      • Lam WL
      • Bruyere H
      • Horsman DE
      • et al.
      Array comparative genomic hybridization of peripheral blood granulocytes of patients with myelodysplastic syndrome detects karyotypic abnormalities.
      ,
      • Stengel A
      • Kern W
      • Haferlach T
      • Meggendorfer M
      • Haferlach C
      The 5q deletion size in myeloid malignancies is correlated to additional chromosomal aberrations and to TP53 mutations.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      ,
      • da Silva FB
      • Machado-Neto JA
      • Bertini V
      • Velloso E
      • Ratis CA
      • Calado RT
      • et al.
      Single-nucleotide polymorphism array (SNP-A) improves the identification of chromosomal abnormalities by metaphase cytogenetics in myelodysplastic syndrome.
      ,
      • Stevens-Kroef MJ
      • Hebeda KM
      • Verwiel ET
      • Kamping EJ
      • van Cleef PH
      • Kuiper RP
      • et al.
      Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      ,
      • Kunze K
      • Gamerdinger U
      • Lessig-Owlanj J
      • Sorokina M
      • Brobeil A
      • Tur MK
      • et al.
      Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis.
      ,
      • Noronha TR
      • Rohr SS
      • Chauffaille Mde L
      Identifying the similarities and differences between single nucleotide polymorphism array (SNPa) analysis and karyotyping in acute myeloid leukemia and myelodysplastic syndromes.
      7MDSLoss7qEZH2, CUX1D, P (Intermediate)1
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Huh J
      • Jung CW
      • Kim HJ
      • Kim YK
      • Moon JH
      • Sohn SK
      • et al.
      Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category.
      ,
      • Thiel A
      • Beier M
      • Ingenhag D
      • Servan K
      • Hein M
      • Moeller V
      • et al.
      Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance.
      ,
      • Merkerova MD
      • Bystricka D
      • Belickova M
      • Krejcik Z
      • Zemanova Z
      • Polak J
      • et al.
      From cryptic chromosomal lesions to pathologically relevant genes: integration of SNP-array with gene expression profiling in myelodysplastic syndrome with normal karyotype.
      ,
      • Starczynowski DT
      • Vercauteren S
      • Telenius A
      • Sung S
      • Tohyama K
      • Brooks-Wilson A
      • et al.
      High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Volkert S
      • Haferlach T
      • Holzwarth J
      • Zenger M
      • Kern W
      • Staller M
      • et al.
      Array CGH identifies copy number changes in 11% of 520 MDS patients with normal karyotype and uncovers prognostically relevant deletions.
      ,
      • Zhang R
      • Kim YM
      • Wang X
      • Li Y
      • Lu X
      • Sternenberger AR
      • et al.
      Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and/or -7/del(7q).
      ,
      • Svobodova K
      • Zemanova Z
      • Lhotska H
      • Novakova M
      • Podskalska L
      • Belickova M
      • et al.
      Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.
      ,
      • Mohamedali A
      • Gaken J
      • Twine NA
      • Ingram W
      • Westwood N
      • Lea NC
      • et al.
      Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes.
      ,
      • Ganster C
      • Shirneshan K
      • Salinas-Riester G
      • Braulke F
      • Schanz J
      • Platzbecker U
      • et al.
      Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS.
      ,
      • Sugimoto Y
      • Sekeres MA
      • Makishima H
      • Traina F
      • Visconte V
      • Jankowska A
      • et al.
      Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
      ,
      • Babushok DV
      • Xie HM
      • Roth JJ
      • Perdigones N
      • Olson TS
      • Cockroft JD
      • et al.
      Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes.
      ,
      • Stevens-Kroef MJ
      • Hebeda KM
      • Verwiel ET
      • Kamping EJ
      • van Cleef PH
      • Kuiper RP
      • et al.
      Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      ,
      • Kunze K
      • Gamerdinger U
      • Lessig-Owlanj J
      • Sorokina M
      • Brobeil A
      • Tur MK
      • et al.
      Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis.
      7MDSCN-LOH7q21.11-qterEZH2, CUX1Recurrent2
      • Gondek LP
      • Tiu R
      • O'Keefe CL
      • Sekeres MA
      • Theil KS
      • Maciejewski JP
      Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML.
      ,
      • Tiu RV
      • Gondek LP
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      • Elson P
      • Huh J
      • Mohamedali A
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      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Heinrichs S
      • Kulkarni RV
      • Bueso-Ramos CE
      • Levine RL
      • Loh ML
      • Li C
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      Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.
      ,
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      From cryptic chromosomal lesions to pathologically relevant genes: integration of SNP-array with gene expression profiling in myelodysplastic syndrome with normal karyotype.
      ,
      • Evans AG
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      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Gondek LP
      • Haddad AS
      • O'Keefe CL
      • Tiu R
      • Wlodarski MW
      • Sekeres MA
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      Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes.
      ,
      • Hu Q
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      • Yang W
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      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Dunbar AJ
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      • Rataul MS
      • Szpurka H
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      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Ganster C
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      • Braulke F
      • Schanz J
      • Platzbecker U
      • et al.
      Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS.
      ,
      • Nowak D
      • Nolte F
      • Mossner M
      • Nowak V
      • Baldus CD
      • Hopfer O
      • et al.
      Genome-wide DNA-mapping of CD34+ cells from patients with myelodysplastic syndrome using 500 K SNP arrays identifies significant regions of deletion and uniparental disomy.
      ,
      • Larsson N
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      • Lassen C
      • Johansson B
      • Fioretos T
      Myeloid malignancies with acquired trisomy 21 as the sole cytogenetic change are clinically highly variable and display a heterogeneous pattern of copy number alterations and mutations.
      7MDSLoss (Monosomy)7Whole ChromosomeD, P (Poor)1
      • Zhang R
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      • Wang X
      • Li Y
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      Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and/or -7/del(7q).
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      Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes.
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      Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes.
      ,
      • Flach J
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      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      ,
      • Babushok DV
      • Xie HM
      • Roth JJ
      • Perdigones N
      • Olson TS
      • Cockroft JD
      • et al.
      Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes.
      ,
      • Stevens-Kroef MJ
      • Hebeda KM
      • Verwiel ET
      • Kamping EJ
      • van Cleef PH
      • Kuiper RP
      • et al.
      Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome.
      ,
      • Xu X
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      ,
      • Barresi V
      • Palumbo GA
      • Musso N
      • Consoli C
      • Capizzi C
      • Meli CR
      • et al.
      Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML.
      ,
      • Kunze K
      • Gamerdinger U
      • Lessig-Owlanj J
      • Sorokina M
      • Brobeil A
      • Tur MK
      • et al.
      Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis.
      8MDSGain (Trisomy)8Whole ChromosomeP (Intermediate)
      Isolated trisomy 8 or del(20q) are not diagnostic of MDS in the absence of morphologic findings of disease.
      1
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Hu Q
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      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Zhang R
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      • Wang X
      • Li Y
      • Lu X
      • Sternenberger AR
      • et al.
      Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and/or -7/del(7q).
      ,
      • Kolquist KA
      • Schultz RA
      • Furrow A
      • Brown TC
      • Han JY
      • Campbell LJ
      • et al.
      Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
      ,
      • Ganster C
      • Shirneshan K
      • Salinas-Riester G
      • Braulke F
      • Schanz J
      • Platzbecker U
      • et al.
      Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS.
      ,
      • Sugimoto Y
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      • Makishima H
      • Traina F
      • Visconte V
      • Jankowska A
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      Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide.
      ,
      • Vercauteren SM
      • Sung S
      • Starczynowski DT
      • Lam WL
      • Bruyere H
      • Horsman DE
      • et al.
      Array comparative genomic hybridization of peripheral blood granulocytes of patients with myelodysplastic syndrome detects karyotypic abnormalities.
      ,
      • Paulsson K
      • Heidenblad M
      • Strombeck B
      • Staaf J
      • Jonsson G
      • Borg A
      • et al.
      High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration.
      ,
      • Babushok DV
      • Xie HM
      • Roth JJ
      • Perdigones N
      • Olson TS
      • Cockroft JD
      • et al.
      Single nucleotide polymorphism array analysis of bone marrow failure patients reveals characteristic patterns of genetic changes.
      ,
      • Stevens-Kroef MJ
      • Hebeda KM
      • Verwiel ET
      • Kamping EJ
      • van Cleef PH
      • Kuiper RP
      • et al.
      Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome.
      ,
      • Kunze K
      • Gamerdinger U
      • Lessig-Owlanj J
      • Sorokina M
      • Brobeil A
      • Tur MK
      • et al.
      Detection of an activated JAK3 variant and a Xq26.3 microdeletion causing loss of PHF6 and miR-424 expression in myelodysplastic syndromes by combined targeted next generation sequencing and SNP array analysis.
      9MDSGain9pJAK2Recurrent3
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Kolquist KA
      • Schultz RA
      • Furrow A
      • Brown TC
      • Han JY
      • Campbell LJ
      • et al.
      Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
      9MDSCN-LOH9pter-p24.2JAK2Recurrent2
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
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      • Yeung CCS
      • McElhone S
      • Chen XY
      • Ng D
      • Storer BE
      • Deeg HJ
      • et al.
      Impact of copy neutral loss of heterozygosity and total genome aberrations on survival in myelodysplastic syndrome.
      ,
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      11MDSLoss11q14.1-q24.3CBLD, P (Very Good)1
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Vercauteren SM
      • Sung S
      • Starczynowski DT
      • Lam WL
      • Bruyere H
      • Horsman DE
      • et al.
      Array comparative genomic hybridization of peripheral blood granulocytes of patients with myelodysplastic syndrome detects karyotypic abnormalities.
      11MDSCN-LOH11q13.3-qterCBLRecurrent2
      • Gondek LP
      • Tiu R
      • O'Keefe CL
      • Sekeres MA
      • Theil KS
      • Maciejewski JP
      Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML.
      ,
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Huh J
      • Jung CW
      • Kim HJ
      • Kim YK
      • Moon JH
      • Sohn SK
      • et al.
      Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category.
      ,
      • Gondek LP
      • Haddad AS
      • O'Keefe CL
      • Tiu R
      • Wlodarski MW
      • Sekeres MA
      • et al.
      Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes.
      ,
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      ,
      • Barresi V
      • Palumbo GA
      • Musso N
      • Consoli C
      • Capizzi C
      • Meli CR
      • et al.
      Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML.
      11MDSGain (Trisomy and q-arm)11 / 11qCBLRecurrent3
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Heinrichs S
      • Kulkarni RV
      • Bueso-Ramos CE
      • Levine RL
      • Loh ML
      • Li C
      • et al.
      Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.
      ,
      • Starczynowski DT
      • Vercauteren S
      • Telenius A
      • Sung S
      • Tohyama K
      • Brooks-Wilson A
      • et al.
      High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      12MDSLoss12pETV6D, P (Good)1
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Heinrichs S
      • Kulkarni RV
      • Bueso-Ramos CE
      • Levine RL
      • Loh ML
      • Li C
      • et al.
      Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.
      ,
      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Volkert S
      • Haferlach T
      • Holzwarth J
      • Zenger M
      • Kern W
      • Staller M
      • et al.
      Array CGH identifies copy number changes in 11% of 520 MDS patients with normal karyotype and uncovers prognostically relevant deletions.
      ,
      • Kolquist KA
      • Schultz RA
      • Furrow A
      • Brown TC
      • Han JY
      • Campbell LJ
      • et al.
      Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
      12MDSCN-LOH12pter-p11.23ETV6Recurrent2
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      13MDSLoss13qRB1D, P (Intermediate)2
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
      Combined comparative genomic hybridization and single-nucleotide polymorphism array detects cryptic chromosomal lesions in both myelodysplastic syndromes and cytopenias of undetermined significance.
      ,
      • Arenillas L
      • Mallo M
      • Ramos F
      • Guinta K
      • Barragan E
      • Lumbreras E
      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      13MDSCN-LOH13q12.3-qterFLT3, RB1Recurrent3
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      ,
      • Flach J
      • Dicker F
      • Schnittger S
      • Schindela S
      • Kohlmann A
      • Haferlach T
      • et al.
      An accumulation of cytogenetic and molecular genetic events characterizes the progression from MDS to secondary AML: an analysis of 38 paired samples analyzed by cytogenetics, molecular mutation analysis and SNP microarray profiling.
      13MDSGain (Trisomy)13Whole ChromosomeRecurrent3
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      14MDSCN-LOH14q24.2-qterCHGARecurrent3
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Huh J
      • Jung CW
      • Kim HJ
      • Kim YK
      • Moon JH
      • Sohn SK
      • et al.
      Different characteristics identified by single nucleotide polymorphism array analysis in leukemia suggest the need for different application strategies depending on disease category.
      ,
      • Gondek LP
      • Haddad AS
      • O'Keefe CL
      • Tiu R
      • Wlodarski MW
      • Sekeres MA
      • et al.
      Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes.
      ,
      • Mohamedali AM
      • Gaken J
      • Ahmed M
      • Malik F
      • Smith AE
      • Best S
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      High concordance of genomic and cytogenetic aberrations between peripheral blood and bone marrow in myelodysplastic syndrome (MDS).
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      • Dunbar AJ
      • Gondek LP
      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
      250 K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.
      16MDSLoss (Monosomy and q-arm)16 / 16qCDH1Recurrent3
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Kolquist KA
      • Schultz RA
      • Furrow A
      • Brown TC
      • Han JY
      • Campbell LJ
      • et al.
      Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
      ,
      • Xu X
      • Johnson EB
      • Leverton L
      • Arthur A
      • Watson Q
      • Chang FL
      • et al.
      The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
      16MDSCN-LOH16q22.1-qterCDH1Recurrent3
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
      ,
      • Nowak D
      • Nolte F
      • Mossner M
      • Nowak V
      • Baldus CD
      • Hopfer O
      • et al.
      Genome-wide DNA-mapping of CD34+ cells from patients with myelodysplastic syndrome using 500 K SNP arrays identifies significant regions of deletion and uniparental disomy.
      17MDSLoss17pTP53P (Poor)1
      • Tiu RV
      • Gondek LP
      • O'Keefe CL
      • Elson P
      • Huh J
      • Mohamedali A
      • et al.
      Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies.
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      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
      ,
      • Zhang R
      • Kim YM
      • Wang X
      • Li Y
      • Lu X
      • Sternenberger AR
      • et al.
      Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and/or -7/del(7q).
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      • Bajaj R
      • Xu F
      • Xiang B
      • Wilcox K
      • Diadamo AJ
      • Kumar R
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      Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia.
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      • Kolquist KA
      • Schultz RA
      • Furrow A
      • Brown TC
      • Han JY
      • Campbell LJ
      • et al.
      Microarray-based comparative genomic hybridization of cancer targets reveals novel, recurrent genetic aberrations in the myelodysplastic syndromes.
      ,
      • Ganster C
      • Shirneshan K
      • Salinas-Riester G
      • Braulke F
      • Schanz J
      • Platzbecker U
      • et al.
      Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS.
      ,
      • Stevens-Kroef MJ
      • Hebeda KM
      • Verwiel ET
      • Kamping EJ
      • van Cleef PH
      • Kuiper RP
      • et al.
      Microarray-based genomic profiling and in situ hybridization on fibrotic bone marrow biopsies for the identification of numerical chromosomal abnormalities in myelodysplastic syndrome.
      17MDSCN-LOH17pter-p11.2TP53Recurrent2
      • Heinrichs S
      • Kulkarni RV
      • Bueso-Ramos CE
      • Levine RL
      • Loh ML
      • Li C
      • et al.
      Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.
      ,
      • Evans AG
      • Ahmad A
      • Burack WR
      • Iqbal MA
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      • Hu Q
      • Chu Y
      • Song Q
      • Yao Y
      • Yang W
      • Huang S
      The prevalence of chromosomal aberrations associated with myelodysplastic syndromes in China.
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      • Tiu RV
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      Topography, clinical, and genomic correlates of 5q myeloid malignancies revisited.
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      • Arenillas L
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      • et al.
      Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
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      • Dunbar AJ
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      • O'Keefe CL
      • Makishima H
      • Rataul MS
      • Szpurka H
      • et al.
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      17MDSCN-LOH17q11.2-qterSRSF2, NF1Recurrent2
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      19MDSCN-LOH19pter-p13.11DNMT1, PRDX2Recurrent3
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      20MDSLoss20qASXL1P (Good)