Cancer Genetics RSS feed: Current Issue. The aim of Cancer Genetics is to publish high quality scientific papers on the cellular, genetic and molecular aspects of cancer, including cancer predisposition and clinical diagnostic applications. Specific areas of interest include descriptions of new chromosomal, molecular or epigenetic alterations in benign and malignant diseases; novel laboratory approaches for identification and characterization of chromosomal rearrangements or genomic alterations in cancer cells; correlation of genetic changes with pathology and clinical presentation; and the molecular genetics of cancer predisposition. To reach a basic science and clinical multidisciplinary audience, we welcome original full-length articles, reviews, meeting summaries, brief reports, and letters to the editor. http://www.cancergeneticsjournal.org/?rss=yesElsevier Inc.en © 2011 Published by Elsevier Inc. All rights reserved. Cancer Genetics2210-776220412December 2011 © 2011 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.cancergeneticsjournal.org/article/PIIS2210776212000099/abstract?rss=yesCover 110.1016/S2210-7762(12)00009-9Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1OFCOFChttp://www.cancergeneticsjournal.org/article/PIIS2210776212000105/abstract?rss=yesEditorial Board10.1016/S2210-7762(12)00010-5Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1IFCIFChttp://www.cancergeneticsjournal.org/article/PIIS2210776211003085/abstract?rss=yesDyskeratosis congenita (DC) is an inherited bone marrow failure syndrome associated with characteristic mucocutaneous features and a variable series of other somatic abnormalities. The disease is heterogeneous at the genetic and clinical levels. Determination of the genetic basis of DC has established that the disease is caused by a number of genes, all of which encode products involved in telomere maintenance, either as part of telomerase or as part of the shelterin complex that caps and protects telomeres. There is overlap at the genetic and clinical levels with other, more common conditions, including aplastic anemia (AA), pulmonary fibrosis (PF), and liver cirrhosis. Although part of the spectrum of disorders known to be associated with DC, it has emerged that mutations in telomere maintenance genes can lead to the development of AA and PF in the absence of other DC features. Here we discuss the genetics of DC and its relationship to disease presentation.The genetics of dyskeratosis congenitaPhilip J. Mason, Monica Bessler10.1016/j.cancergen.2011.11.002Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1Review635645http://www.cancergeneticsjournal.org/article/PIIS2210776211003024/abstract?rss=yesChromosomal aberrations are a hallmark of human papillomavirus (HPV)-induced cervical carcinogenesis. The aim of this project was to identify structural chromosomal aberrations which may be characteristic for intraepithelial neoplasias (CIN) and cervical carcinomas (CxCa). Two independent HPV16 immortalized keratinocyte cell lines (HPKIA, HPKII) were used as a cell culture model system for cervical carcinogenesis. Different passages of HPKIA and HPKII were analyzed by multicolor spectral karyotyping. Several chromosomal translocations were identified in HPK cells and were validated by interphase fluorescence in situ hybridization (I-FISH). Three unbalanced whole chromosome arm translocations, der(10;14), der(7;21), and der(7;12), were cell line specific. The presence and frequency of these translocations were then examined by I-FISH in frozen tissue sections from normal cervical epithelia (n=6), CIN2/3 (n=15), and CxCa (n=15). The der(10;14) and der(7;21) were detected in 80% and 53.3% of CIN2/3, and in 60% and 46.7% of CxCa, respectively. The percentage of nuclei with translocations in individual lesions was significantly higher among CxCa. The der(7;12) could only be detected in 27% of CIN2/3. None of the translocations were detected in normal cervical epithelia. The translocated chromosomes may contribute to the clonal expansion of subpopulations in these cases and may thus be of diagnostic relevance.Two novel unbalanced whole arm translocations are frequently detected in cervical squamous cell carcinomaClaudia Backsch, Birgit Pauly, Melanie Liesenfeld, Cornelia Scheungraber, Mieczyslaw Gajda, Kristin Mrasek, Thomas Liehr, Andreas Clad, Evelin Schrock, Ingo B. Runnebaum, Matthias Dürst10.1016/j.cancergen.2011.10.009Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1Original articles646653http://www.cancergeneticsjournal.org/article/PIIS221077621100305X/abstract?rss=yesChronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease. The methods currently used for monitoring CLL and determining conditions for treatment are limited in their ability to predict disease progression, patient survival, and response to therapy. Although clonal diversity and the acquisition of new chromosomal abnormalities during the disease course (clonal evolution) have been associated with disease progression, their prognostic potential has been underappreciated because cytogenetic and fluorescence in situ hybridization (FISH) studies have a restricted ability to detect genomic abnormalities and clonal evolution. We hypothesized that whole genome analysis using high resolution single nucleotide polymorphism (SNP) microarrays would be useful to detect diversity and infer clonal evolution to offer prognostic information. In this study, we used the Infinium Omni1 BeadChip (Illumina, San Diego, CA) array for the analysis of genetic variation and percent mosaicism in 25 non-selected CLL patients to explore the prognostic value of the assessment of clonal diversity in patients with CLL. We calculated the percentage of mosaicism for each abnormality by applying a mathematical algorithm to the genotype frequency data and by manual determination using the Simulated DNA Copy Number (SiDCoN) tool, which was developed from a computer model of mosaicism. At least one genetic abnormality was identified in each case, and the SNP data was 98% concordant with FISH results. Clonal diversity, defined as the presence of two or more genetic abnormalities with differing percentages of mosaicism, was observed in 12 patients (48%), and the diversity correlated with the disease stage. Clonal diversity was present in most cases of advanced disease (Rai stages III and IV) or those with previous treatment, whereas 9 of 13 patients without detected clonal diversity were asymptomatic or clinically stable. In conclusion, SNP microarray studies with simultaneous evaluation of genomic alterations and mosaic distribution of clones can be used to assess apparent clonal evolution via analysis of clonal diversity. Since clonal evolution in CLL is strongly correlated with disease progression, whole genome SNP microarray analysis provides a new comprehensive and reliable prognostic tool for CLL patients.Clonal diversity analysis using SNP microarray: a new prognostic tool for chronic lymphocytic leukemiaLinsheng Zhang, Iya Znoyko, Luciano J. Costa, Laura K. Conlin, Robert D. Daber, Sally E. Self, Daynna J. Wolff10.1016/j.cancergen.2011.10.012Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1Original articles654665http://www.cancergeneticsjournal.org/article/PIIS2210776211003395/abstract?rss=yesChondromyxoid fibroma (CMF) is a rare cartilaginous tumor of bone. It typically presents in the long tubular bones and to a lesser extent in the small bones of the hands and feet of young adults. To date, several cytogenetic abnormalities have been described in association with CMF. We studied a phalangeal CMF from a 13-year-old female by cytogenetic methods. We found a novel unbalanced translocation between the long arms of chromosomes 1 and 9, resulting in loss of 1p. In addition, rearrangements involving the 6q23 and 9q22 regions were also observed. To our knowledge, this is the first report in the literature describing this novel chromosomal translocation in CMF.A t(1;9)(q10;q10) translocation with additional 6q23 and 9q22 rearrangements in a case of chondromyxoid fibromaTahereh Dadfarnia, Gopalrao V.N. Velagaleti, Kelly D. Carmichael, Eduardo Eyzaguirre, Mahmoud A. Eltorky, Suimin Qiu10.1016/j.cancergen.2011.11.005Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1Original articles666670http://www.cancergeneticsjournal.org/article/PIIS2210776211003413/abstract?rss=yesEpithelioid hemangioendothelioma (EHE) is a rare vascular tumor whose pathological diagnosis can be difficult. In the literature two cases of EHE were found to harbor a balanced t(1;3)(p36.3;q25) translocation, suggesting a characteristic chromosomal rearrangement as cause for the development of EHE. In this study, 14 cases of EHE were investigated by interphase fluorescence in situ hybridization (FISH) directed against the translocation breakpoint 1p36.3. A subset of cases was also analyzed by comparative genomic hybridization (CGH) and image cytometry. Five out of eight cases that could be successfully analyzed by FISH harbored a chromosomal break in the 1p36.3 region. The break-apart signals were present in diploid nuclei, and less frequently also in tetraploid nuclei. In the latter, the chromosomal break was present twice, suggesting that polyploidy occurred after the chromosomal alteration. DNA cytometry confirmed that tetraploid cells were present in most examined cases with one case indicating almost equal amounts of diploid and tetraploid tumor cells. CGH revealed single chromosomal imbalances of unclear significance. We could confirm that EHE may harbor a recurrent mutation involving the 1p36.3 chromosomal region thus supporting the notion that the t(1;3)(p36.3;q25) translocation is a relevant genetic finding in this tumor entity.Molecular cytogenetic characterization of epithelioid hemangioendotheliomaCornelius Woelfel, Thomas Liehr, Anja Weise, Jan Langrehr, Waleed Amin Kotb, Manuela Pacyna-Gengelbach, Detlef Katenkamp, Iver Petersen10.1016/j.cancergen.2011.11.007Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1Original articles671676http://www.cancergeneticsjournal.org/article/PIIS2210776211003061/abstract?rss=yesSecondary peripheral chondrosarcoma is a malignant chondroid tumor arising in a benign precursor, either an osteochondroma or an enchondroma. Multiple osteochondromas syndrome (MO) is an autosomal dominant skeletal disorder associated with bony growths in the form of osteochondromas that occasionally undergo malignant transformation to secondary peripheral chondrosarcomas. We describe the genetic examination of three secondary peripheral chondrosarcomas that had arisen synchronously from osteochondromas in a patient with MO by chromosome banding, high resolution chromosomal comparative genomic hybridization, and mutation analysis of the EXT1 and EXT2 genes. In two of the tumors (the third was not genetically informative), very similar chromosome abnormalities were found, indicating that they must somehow be part of the same neoplastic process in spite of being anatomically distinct.Similar cytogenetic findings in two synchronous secondary peripheral chondrosarcomas in a patient with multiple osteochondromasAnastasios I. Kyriazoglou, Efthimios Dimitriadis, Niki Arnogiannaki, Petter Brandal, Sverre Heim, Nikos Pandis10.1016/j.cancergen.2011.10.013Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1Brief communications677681http://www.cancergeneticsjournal.org/article/PIIS2210776211003371/abstract?rss=yesSingle nucleotide polymorphism array (SNP-A)-based karyotyping can identify copy-neutral loss of heterozygosity (CN-LOH) as well as cryptic lesions not detected by metaphase cytogenetics. We report serial genetic studies on a patient diagnosed with chronic myelomonocytic leukemia who progressed to acute leukemia. Monosomy 7 was predominantly found at diagnosis, but clones changed to CN-LOH of chromosome 7 with disease progression. Furthermore, subclones with genomic aberrations of 3q gain, 1p CN-LOH, and trisomy 12 newly appeared, suggesting that they were also involved in the transformation process. Additionally, by SNP-A, a presumably balanced translocation, t(14;20), identified by metaphase cytogenetics, was shown to result in an unbalanced 20q deletion at the breakpoint. The sequential changes identified by SNP-A may provide a better understanding of the mechanism of clonal evolution.Single nucleotide polymorphism array-based karyotyping shows sequential genomic changes from monosomy to copy-neutral loss of heterozygosity of chromosome 7 and 20q deletion within a balanced translocation t(14;20) in AMLJungwon Huh, Yeung Chul Mun, Chu Myong Seong, Wha Soon Chung10.1016/j.cancergen.2011.11.003Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1Brief communications682686http://www.cancergeneticsjournal.org/article/PIIS2210776211003401/abstract?rss=yesA translocation between chromosomes 19 and 21 [dic/t(19;21)(p13;v)] is very rare. To date, only three cases of this particular chromosomal abnormality have been reported. The translocations in these three cases were secondary changes in acute lymphoblastic leukemia (ALL) patients with the t(9;22) translocation. The gene(s) at the breakpoints of either chromosome 19p13 or 21q have not yet been identified. Here, we present a case study of a 21-year-old female with a diagnosis of precursor B cell ALL, with the t(9;22) translocation and secondary changes including a der(19)t(19;21) and an extra Philadelphia (Ph+) chromosome [der(22)t(9;22)]. Array comparative genomic hybridization (aCGH) analysis identified UHRF1 and NRIP1 as genes that were interrupted at the breakpoints of 19p13.3 and 21q21.1, and joined together as a possible fusion gene, 5′-NRIP1/UHRF1-3′, on the derivative chromosome 19. To our knowledge, this is the first description of possible genes involved in the unbalanced translocation between chromosomes 19 and 21 in a patient with an ALL-positive for a t(9;22) translocation.A possible 5′-NRIP1/UHRF1-3′ fusion gene detected by array CGH analysis in a Ph+ ALL patientRui Zhang, Young Mi Kim, Xiaohe Yang, Yan Li, Shibo Li, Ji-Yun Lee10.1016/j.cancergen.2011.11.006Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1Brief communications687691http://www.cancergeneticsjournal.org/article/PIIS2210776211003383/abstract?rss=yesImatinib mesylate (IM) is the first tyrosine kinase inhibitor (TKI) introduced for the treatment of chronic myelogenous leukemia (CML) with remarkable high rates of complete hematologic and cytogenetic response and an acceptable safety and toxicity profile. Clonal aberrations (CAs) in Philadelphia (Ph)-chromosome negative metaphases have been reported in patients with CML after treatment with IM, with a varying frequency between series (1.6–20.6%) . Most CAs are numerical aberrations, whereas structural aberrations, in particular, balanced translocations are much less frequent .Sequential transient novel chromosomal translocations in a patient with chronic myelogenous leukemia in complete cytogenetic remission after therapy with imatinib mesylateGeorge Papaioannou, Anastasia Athanasiadou, Georgia Voutiadou, Maria Gaitatzi, Ioannis Batsis, Tasoula Touloumenidou, Achilles Anagnostopoulos10.1016/j.cancergen.2011.11.004Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1Letter to the editor692693http://www.cancergeneticsjournal.org/article/PIIS2210776211003681/abstract?rss=yesOliver A. Hampton, Maxim Koriabine, Christopher A. Miller, Cristian Coarfa, Jian Li, Petra Den Hollander, Caroline Schoenherr, Lucia Carbone, Mikhail Nefedov, Boudewijn F.H. Ten Hallers, Adrian V. Lee, Pieter J. De Jong, Aleksandar Milosavljevic. Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines. Cancer Genetics 2011;204:447–457.Erratum: Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines10.1016/j.cancergen.2011.12.004Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1Erratum694694http://www.cancergeneticsjournal.org/article/PIIS2210776212000117/abstract?rss=yesTable of Contents10.1016/S2210-7762(12)00011-7Cancer Genetics 204, 12 (2011)2011-12-01Cancer Genetics2011-12-0120412S2210-7762(11)X0012-1FrontmatterA1A2