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Cited by 4 publications
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Most cancer cells have acquired clonal chromosome abnormalities. An increasing number of characteristic aberrations, in particular balanced changes, are with remarkable specificity associated with distinctive morphological and clinical disease characteristics. The identification of these recurrent aberrations has several important implications. First, cytogenetics has become an increasingly important tool in the clinical management of cancer patients to help establish a correct diagnosis, to predict prognosis and to select the most appropriate treatment. Second, the cytogenetic information has provided invaluable help to identify genes of importance in the carcinogenic process by focusing the attention to chromosomal sites that may harbour genes which when rearranged lead to neoplasia. Practically, all balanced structural rearrangements that have been characterised at the molecular level have been found to exert their action through one of the two alternative mechanisms: deregulation, usually overexpression, of a seemingly normal gene in one of the breakpoints, or the creation of an abnormal hybrid gene through fusion of parts of two genes, one in each breakpoint. Key Concepts Chromosome aberrations are a characteristic feature of neoplasia. Chromosome abnormalities have been reported in almost 70 000 human neoplasms. Recurrent balanced chromosome rearrangements, in particular translocations, are associated with distinctive tumour characteristics. Cancer‐associated chromosome changes are of clinical importance for diagnosis, prognosis and treatment. The breakpoints of balanced structural chromosome aberrations point at the locations of cancer‐relevant genes. Cancer‐associated structural chromosome abnormalities lead to the formation of hybrid genes through fusions of parts of two genes located in the breakpoints. Almost 800 gene fusions created by an acquired chromosome change are known.
Most cancer cells have acquired clonal chromosome abnormalities. An increasing number of characteristic aberrations, in particular balanced changes, are with remarkable specificity associated with distinctive morphological and clinical disease characteristics. The identification of these recurrent aberrations has several important implications. First, cytogenetics has become an increasingly important tool in the clinical management of cancer patients to help establish a correct diagnosis, to predict prognosis and to select the most appropriate treatment. Second, the cytogenetic information has provided invaluable help to identify genes of importance in the carcinogenic process by focusing the attention to chromosomal sites that may harbour genes which when rearranged lead to neoplasia. Practically, all balanced structural rearrangements that have been characterised at the molecular level have been found to exert their action through one of the two alternative mechanisms: deregulation, usually overexpression, of a seemingly normal gene in one of the breakpoints, or the creation of an abnormal hybrid gene through fusion of parts of two genes, one in each breakpoint. Key Concepts Chromosome aberrations are a characteristic feature of neoplasia. Chromosome abnormalities have been reported in almost 70 000 human neoplasms. Recurrent balanced chromosome rearrangements, in particular translocations, are associated with distinctive tumour characteristics. Cancer‐associated chromosome changes are of clinical importance for diagnosis, prognosis and treatment. The breakpoints of balanced structural chromosome aberrations point at the locations of cancer‐relevant genes. Cancer‐associated structural chromosome abnormalities lead to the formation of hybrid genes through fusions of parts of two genes located in the breakpoints. Almost 800 gene fusions created by an acquired chromosome change are known.
Chromosomal translocations in chronic lymphocytic leukemia (CLL) are very rare, and therefore systematic analysis of large series of cases is needed to allow the identification of recurrent rearrangements, breakpoints involved, and target genes.The aims of the present study were to identify new translocations and their clinical impact and to establish their frequency in a large cohort of 2843 CLL patients. By conventional cytogenetics 250 translocations were identified in 215 (7.5%) patients, 186 (74%) were apparently balanced and 64 (26%) were unbalanced. All chromosomes were involved in translocations, except Y chromosome. The chromosomes more frequently translocated were in decreasing frequency chromosomes 14, 18, 13, 17, 1, 6, 2, 3, 8, and 11. Translocations were found in the karyotypes either as the unique chromosomal abnormality (27%), associated with another alteration (24%), or as a part of a complex karyotype (CK, 48%). A large proportion of rearranged breakpoints involved genes related to CLL such as IGH (14q32), RB1, MIR15A, MIR16-1 (13q14), BCL2 (18q21), IGL (22q11.2), TP53 (17p13), IRF4 (6p25-p23), ATM (11q22), and CDK6 (7q21). Overall, 76 novel CLL translocations were identified, including a recurrent t(8;11) (p21;q21-23). Whole-genome sequencing and/or copy-number microarray data of 24 cases with translocations confirmed all rearrangements, enabled refinement of 3 karyotypes and all breakpoints at gene level. The projected survival and time to first treatment significantly decreased linearly with the number of translocations. In summary, this study allowed to establish the frequency of translocations (7.5%) and to identify new translocations in a cohort of 2843 CLL patients.
Seven oncogenic viruses are known for tumorigenesis and contribute to 12% of all human cancers. The oncogenic factors, the target tissue, and pathology of cancer vary among these viruses with several mechanisms proposed for the initiation and development of cancer. Aneuploidy in cells is associated with anomalies in chromosome number that can be a hallmark of cancer, a disease defined by expanded proliferative potential. In this review, we summarize the different mechanisms of aneuploidy and furthermore discuss recent findings of the role of viral oncoproteins in inducing cellular aneuploidy that might facilitate tumorigenesis. Improved understanding of viral oncogenesis may help to find new strategies for controlling virus-associated cancers. KEYWORDS aneuploidy, cancer, virusThe key to precise segregation of chromosomes is that they should be correctly attached at the bipolar spindle, with sister kinetochore binding microtubules emanating from opposite spindle poles. Defects in kinetochore-microtubule (KT-MT) attachments in somatic cells cause segregation error and aneuploidy. [9][10][11] Abbreviations: KT-MT, kinetochore-microtubule; SAC, spindle assembly checkpoint; MCC, mitotic checkpoint complex; CPC, chromosomal passenger complex; BFB, breakage-fusionbridge; DSB, double-stranded break; HR, high risk; HCC, hepatocellular carcinoma; HBx, HBV X protein; LHBS, large surface antigen; AURKB, Aurora B kinase; LMP1, latent membrane protein 1; TK, thymidine kinase; HTLV-1, human T cell leukemia virus type 1;ATL, adult T cell leukemia/lymphoma; HBZ, basic leucine zipper factor; RanBP1, Ranspecific binding protein 1; NHEJ, nonhomologous end joining; ST, small tumor antigen;MEFs, mouse embryo fibroblasts
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