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Genes 2013, 4(4), 536-555; doi:10.3390/genes4040536
Article

Copy Number Variation in Hereditary Non-Polyposis Colorectal Cancer

1,2
, 1,2, 1,2
, 1,3
, 3
, 3
 and 1,2,4,*
1 Information Based Medicine Program, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, 2305, Australia 2 School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, New South Wales, 2308, Australia 3 CSIRO Preventative Health Flagship and Division of Animal, Food and Health Sciences, North Ryde, New South Wales, 2113, Australia 4 Division of Molecular Medicine, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, New South Wales, 2305, Australia
* Author to whom correspondence should be addressed.
Received: 26 July 2013 / Revised: 2 September 2013 / Accepted: 11 September 2013 / Published: 26 September 2013
(This article belongs to the Special Issue Microsatellite Instability)
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Abstract

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.
Keywords: microsatellite instability (MSI); cancer; DNA repair; diagnostic testing; HNPCC/Lynch Syndrome; copy number variation; affymetrix; array microsatellite instability (MSI); cancer; DNA repair; diagnostic testing; HNPCC/Lynch Syndrome; copy number variation; affymetrix; array
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Masson, A.L.; Talseth-Palmer, B.A.; Evans, T.-J.; Grice, D.M.; Duesing, K.; Hannan, G.N.; Scott, R.J. Copy Number Variation in Hereditary Non-Polyposis Colorectal Cancer. Genes 2013, 4, 536-555.

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