Advertisement

Detecting the “undetectable” alterations: Use of NGS to uncover high-risk alterations

      Abstract

      Copy number variants are common in patients with myeloid malignancies and may confer diagnostic, prognostic or therapeutic relevance. However, detection of these variants may require multiple testing modalities, which may not be available or ordered on all cases. We present a case that highlights the efficacy of copy number analysis by next generation sequencing to identify clinically relevant variants that may otherwise be missed by conventional cytogenetics and typical florescent in situ hybridization panels.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Cancer Genetics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Shen W.
        • Szankasi P.
        • Sederberg M.
        • et al.
        Concurrent detection of targeted copy number variants and mutations using a myeloid malignancy next generation sequencing panel allows comprehensive genetic analysis using a single testing strategy.
        Br J Haematol. 2016; 173 ([published Online First: Epub Date]): 49-58https://doi.org/10.1111/bjh.13921
        • Mohamedali A.
        • Gaken J.
        • Twine N.A.
        • et al.
        Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes.
        Blood. 2007; 110 ([published Online First: Epub Date]): 3365-3373https://doi.org/10.1182/blood-2007-03-079673
        • Arenillas L.
        • Mallo M.
        • Ramos F.
        • et al.
        Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.
        Genes Chromosomes Cancer. 2013; 52 ([published Online First: Epub Date]): 1167-1177https://doi.org/10.1002/gcc.22112
        • Walter M.J.
        • Payton J.E.
        • Ries R.E.
        • et al.
        Acquired copy number alterations in adult acute myeloid leukemia genomes.
        Proc Natl Acad Sci U S A. 2009; 106 ([published Online First: Epub Date]): 12950-12955https://doi.org/10.1073/pnas.0903091106
        • Xu X.
        • Johnson E.B.
        • Leverton L.
        • et al.
        The advantage of using SNP array in clinical testing for hematological malignancies–a comparative study of three genetic testing methods.
        Cancer Genet. 2013; 206 ([published Online First: Epub Date]): 317-326https://doi.org/10.1016/j.cancergen.2013.09.001
        • Kluk M.J.
        • Lindsley R.C.
        • Aster J.C.
        • et al.
        Validation and implementation of a custom next-generation sequencing clinical assay for hematologic malignancies.
        J Mol Diagn. 2016; 18 ([published Online First: Epub Date]): 507-515https://doi.org/10.1016/j.jmoldx.2016.02.003
        • Huh Y.O.
        • Tang G.
        • Talwalkar S.S.
        • et al.
        Double minute chromosomes in acute myeloid leukemia, myelodysplastic syndromes, and chronic myelomonocytic leukemia are associated with micronuclei, MYC or MLL amplification, and complex karyotype.
        Cancer Genet. 2016; 209 ([published Online First: Epub Date]): 313-320https://doi.org/10.1016/j.cancergen.2016.05.072
        • Abbate A.
        • Tolomeo D.
        • Cifola I.
        • et al.
        MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences.
        Leukemia. 2018; 32 ([published Online First: Epub Date]): 2152-2166https://doi.org/10.1038/s41375-018-0033-0
        • Stephens P.J.
        • Greenman C.D.
        • Fu B.
        • et al.
        Massive genomic rearrangement acquired in a single catastrophic event during cancer development.
        Cell. 2011; 144 ([published Online First: Epub Date]): 27-40https://doi.org/10.1016/j.cell.2010.11.055
        • Gao J.
        • Chen Y.H.
        • Mina A.
        • et al.
        Unique morphologic and genetic characteristics of acute myeloid leukemia with chromothripsis: a clinicopathologic study from a single institution.
        Hum Pathol. 2020; 98 ([published Online First: Epub Date]): 22-31https://doi.org/10.1016/j.humpath.2020.02.003
        • Vetro C.
        • Haferlach T.
        • Meggendorfer M.
        • et al.
        Cytogenetic and molecular genetic characterization of KMT2A-PTD positive acute myeloid leukemia in comparison to KMT2A-Rearranged acute myeloid leukemia.
        Cancer Genet. 2020; 240 ([published Online First: Epub Date]): 15-22https://doi.org/10.1016/j.cancergen.2019.10.006
        • Hinai A.
        • Pratcorona M.
        • Grob T.
        • et al.
        The landscape of KMT2A-PTD AML: concurrent mutations, gene expression signatures, and clinical outcome.
        Hemasphere. 2019; 3 ([published Online First: Epub Date]): e181https://doi.org/10.1097/HS9.0000000000000181
        • Mims A.S.
        • Mishra A.
        • Orwick S.
        • et al.
        A novel regimen for relapsed/refractory adult acute myeloid leukemia using a KMT2A partial tandem duplication targeted therapy: results of phase 1 study NCI 8485.
        Haematologica. 2018; 103 ([published Online First: Epub Date]): 982-987https://doi.org/10.3324/haematol.2017.186890