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Hereditary non‐polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations
Author(s) -
Thompson E,
Meldrum CJ,
Crooks R,
McPhillips M,
Thomas L,
Spigelman AD,
Scott RJ
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.1399-0004.2004.00214.x
Subject(s) - dna mismatch repair , genetics , colorectal cancer , gene , mutation , cancer , medicine , biology
Hereditary non‐polyposis colorectal cancer (HNPCC) is an autosomal dominant, inherited condition that is characterized primarily by the development of early‐onset colorectal cancer and a number of other epithelial malignancies. The underlying genetic basis of the disease is associated with a breakdown of DNA‐mismatch repair. There are many genes involved in DNA‐mismatch repair, and five of them have been implicated in HNPCC. Two of the genes ( hMSH2 and hMLH1 ) account for the majority of HNPCC families (approximately 60%), and it is not known what the exact contributions of the remaining three genes ( hPMS1 , hPMS2 , and hMSH6 ) are in relation to this condition. In addition, a sixth gene ( hEXO1 ) has been associated with a disease phenotype that is consistent with HNPCC. Current estimates suggest that all four of these genes, combined, may account for up to 5% of families. In this report, we examine the contribution of hPMS2 and hEXO1 to a well‐defined set of families that fulfill the diagnostic criteria for HNPCC. The genes, hPMS2 and hEXO1 , were studied by denaturing high performance liquid chromatography (DHPLC) analysis in 21 families that have previously been determined not to have mutations in hMSH2 or hMLH1 . hPMS2 accounts for a small proportion of HNPCC families, and none were deemed to be associated with hEXO1 . Mutations in hPMS2 appear to account for a small proportion of families adhering to the Amsterdam II criteria, whereas hEXO1 does not appear to be associated with HNPCC.