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Family cancer histories predictive of a high risk of hereditary non‐polyposis colorectal cancer associate significantly with a genomic rearrangement in hMSH2 or hMLH1
Author(s) -
Ainsworth PJ,
Koscinski D.,
Fraser BP,
Stuart JA
Publication year - 2004
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.0009-9163.2004.00282.x
Subject(s) - multiplex ligation dependent probe amplification , proband , genetics , dna mismatch repair , germline mutation , colorectal cancer , biology , mutation , cancer , exon , medicine , gene
Hereditary non-polyposis colorectal cancer (HNPCC) results from inactivating germline mutations in a set of DNA-mismatch-repair genes, of which the most clinically relevant are hMSH2 and hMLH1. Computer-assisted pedigree risk assessment tools are available to assist in the calculation of an individual's likelihood of bearing such a deleterious mutation. One such tool, cancergene version 3.4 (http://www3.utsouthwestern.edu/cancergene) was used to assess the risk of a deleterious mutation in the genes hMSH2 and/or hMLH1 in a series of probands selected from a panel of 67 South-western Ontario kindred previously identified as likely candidates for HNPCC by established clinical criteria. A DNA sample isolated from peripheral blood leukocytes obtained from each of these probands was examined for genomic rearrangement using the multiplex ligation-dependent probe amplification (MLPA) method. Of the individuals calculated to have a risk of >50% of a hMSH2 or hMLH1 gene mutation by the CancerGene risk assessment tool, 69% (9/13) were shown to have a genomic rearrangement resulting in the deletion of one or more exons of one of these two genes. Family cancer histories predictive of a high risk of HNPCC significantly associate with a genomic rearrangement in hMSH2 or hMLH1.