. "Germline mutations in MSH6 can cause HNPCC, which is associated with a tumor phenotype featuring MSI. However, tumors arising in persons with disease-causing mutations of MSH6 may or may not exhibit MSI. We used D-HPLC to screen for germline mutations in the promoter region, the coding region and the 3'-UTR of MSH6. Eighty-four families, enrolled on the basis of Amsterdam I and II criteria (HNPCC families) and less stringent criteria (HNPCC-like families), were tested for MMR gene mutations; 27 families had a disease-causing mutation in MLH1 or MSH2, and the remaining 57 families were tested for mutations in MSH6. Two protein-truncating mutations were identified in each of 2 families fulfilling the Amsterdam I criteria, being present in persons affected with early-onset colorectal cancers exhibiting MSI. Immunohistochemical analysis showed that expression of both MSH2 and MSH6 proteins was lost in the cancer cells of the 2 mutation carriers but only MSH6 protein expression was lost in 2 adenomatous polyps. A third possibly disease-causing mutation was found in a person affected with a tumor that did not exhibit MSI. In addition, we found 4 new polymorphisms and determined that neither of the 2 studied by association analysis conferred susceptibility to colorectal or endometrial cancer. Altogether, our results indicate that disease-causing germline mutations of MSH6 are rare in HNPCC and HNPCC-like families." . . "Int. J. Cancer" . "Nafa K." . "Ellis N.A." . "Ye T.Z." . "Offit K." . "Markowitz A.J." . "Lerman G.S." . "Kolachana P." . "Guillem J.G." . "Shia J." . "Glogowski E." . "Peterlongo P." . "Boyd J.A." . "2003"^^ . "571-579" . "MSH6 germline mutations are rare in colorectal cancer families." . "107" . "doi:10.1002/ijc.11415" .