Copy Number Variation in Hereditary Non-Polyposis Colorectal Cancer

Genes

Amy L. Masson¹  Bente A. Talseth-Palmer¹  Tiffany-Jane Evans¹  Desma M. Grice¹  Konsta Duesing²  Garry N. Hannan² 

[1] Information Based Medicine Program, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, 2305, Australia; E-Mails:;CSIRO Preventative Health Flagship and Division of Animal, Food and Health Sciences, North Ryde, New South Wales, 2113, Australia; E-Mails:

关键词: microsatellite instability (MSI);    cancer;    DNA repair;    diagnostic testing;    HNPCC/Lynch Syndrome;    copy number variation;    affymetrix;    array;   

DOI  :  10.3390/genes4040536

来源: mdpi

【 摘 要 】

Hereditary non-polyposis colorectal cancer (HNPCC) is the commonest form of inherited colorectal cancer (CRC) predisposition and by definition describes families which conform to the Amsterdam Criteria or reiterations thereof. In ~50% of patients adhering to the Amsterdam criteria germline variants are identified in one of four DNA Mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Loss of function of any one of these genes results in a failure to repair DNA errors occurring during replication which can be most easily observed as DNA microsatellite instability (MSI)—a hallmark feature of this disease. The remaining 50% of patients without a genetic diagnosis of disease may harbour more cryptic changes within or adjacent to MLH1, MSH2, MSH6 or PMS2 or elsewhere in the genome. We used a high density cytogenetic array to screen for deletions or duplications in a series of patients, all of whom adhered to the Amsterdam/Bethesda criteria, to determine if genomic re-arrangements could account for a proportion of patients that had been shown not to harbour causative mutations as assessed by standard diagnostic techniques. The study has revealed some associations between copy number variants (CNVs) and HNPCC mutation negative cases and further highlights difficulties associated with CNV analysis.

【 授权许可】

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© 2013 by the authors; licensee MDPI, Basel, Switzerland.