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• W2060391238 endingPage "153" @default.
• W2060391238 startingPage "148" @default.
• W2060391238 abstract "Positional cloning and linkage analysis have shown that inactivation of one of the mismatch repair genes (hMLH1, hMSH2, hPMS1, hPMS2, GTBP/hMSH6) is responsible for the microsatellite instability or replication error (RER+) seen in more than 90% of hereditary non-polyposis colorectal cancers (HNPCC) and 15% of sporadic RER+ colorectal cancers. In HNPCC, a germline mutation (usually in hMLH1 or hMSH2) is accompanied by one further event (usually allelic loss) to inactivate a mismatch repair gene. In contrast, somatic mutations in the mismatch repair genes are not frequently found in sporadic RER+ colorectal cancers. Hypermethylation of the hMLH1 promoter region has recently been described, and this epigenetic change is the predominant cause of inactivation of mismatch repair genes in sporadic RER+ colorectal and other cancers. Inactivation of a mismatch repair gene may occur early (before inactivation of the APC gene) and produce a raised mutation rate in a proportion of HNPCC patients, and these cancers will follow a different pathway to other RER+ cancers. However, it is likely that selection for escape from apoptosis is the most important feature in the evolution of an RER+ cancer.Long before molecular genetics had given us insight into the aetiology of colorectal cancer, Dr Aldred Warthin, professor of pathology at the University of Michigan, Ann Arbor, had described several families who appeared to have a predisposition to cancer.1 2 In 1895, Dr Warthin's seamstress had commented that she would die of gastric, colon, or uterine cancer. She stated that most of her relatives had died from these conditions and she did indeed die from endometrial carcinoma at a young age.In 1966, Dr Henry Lynch from Omaha, Nebraska, and Dr Marjorie Shaw from Ann Arbor, Michigan, published the findings of two large families (family “N” from Nebraska and family “M” from Michigan) that had …" @default.
• W2060391238 created "2016-06-24" @default.
• W2060391238 creator A5012720076 @default.
• W2060391238 creator A5049383372 @default.
• W2060391238 creator A5079579104 @default.
• W2060391238 date "2000-07-01" @default.
• W2060391238 modified "2023-10-18" @default.
• W2060391238 title "DNA mismatch repair genes and colorectal cancer" @default.
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