HNPCC Info

copied from the sloan-ketterington hospital page December 26, 2013:   Important Information for Those Who Have Had Colon Cancer Testing prior to November 2004 If you underwent genetic testing for colorectal cancer prior to November 2004, and the results were negative, you may wish to consider undergoing new tests that have become available since then.For genetic testing of the MLH1, MSH2, and APC genes, a test called Southern blot is now available that looks for gene changes in which large portions of a gene may be missing or rearranged. There is a possibility that your previous genetic tests may not have detected such mutations, if they are present.In addition, three genes that predispose to colorectal cancer – PMS2, MSH6, and MUTYH – have been identified in recent years, and new genetic tests are available to test for mutations in these genes.  

2006: DNA mismatch repair genes and colorectal cancer. J M Wheeler, W F Bodmer, and N J Mortensen Gut 47 (1), 148-53 (Jul 2000) info:pmid/10861278 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. Inacti...