These data indicate that breast cancer may result from the inheritance of a mutant MMR gene, and that breast cancer may occur as an integral tumor in the HNPCC syndrome.
The majority of HNPCC families have germline mutations in mismatch repair (MMR) genes, such as MSH2 or MLH1, so that HNPCC cancers characteristically exhibit DNA replication errors (RERs) at microsatellite loci.
Abnormalities in at least one of five mismatch repair (MMR) genes are implicated in the development of cancers in hereditary nonpolyposis colon cancer and the associated MIN.
Germline mutations of MMR genes cause susceptibility to a hereditary form of colon cancer, hereditary nonpolyposis colon cancer (HNPCC), which represents one of the most common syndromes associated with cancer predisposition in man.
Microsatellite instability (MSI) is intrinsic to most colorectal carcinomas (CRC) from patients with hereditary nonpolyposis colorectal cancer (HNPCC), reflecting germline mutations in the mismatch-repair (MMR) genes.
Microsatellite instability (MIN) due to defective mismatch repair (MMR) genes has been reported in a subset of sporadic colorectal carcinomas and in the majority of tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.
Although the results of this study were inconclusive because of the small sample size and use of prevalent cases, it is biologically plausible that patients with colorectal cancers may have a lower expression of MMR genes than healthy controls because malfunction of these genes has been shown in hereditary nonpolyposis colon cancer.
Thus, MSI and germline MMR gene mutation is present in a subset of young glioma patients, and these patients and their family members are at risk of developing other hereditary nonpolyposis colorectal cancer syndrome-related tumors, in particular colorectal carcinomas.
Mutations in mismatch repair (MMR) genes have been associated with genomic instability in several human cancers, such as those of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.
While the MSI+ phenotype observed in endometrial tumors from HNPCC patients is attributed to germ line mutations in mismatch repair (MMR) genes, somatic mutations of known MMR genes are infrequent in MSI+ sporadic endometrial carcinomas.
Hereditary nonpolyposis colon cancer is a common hereditary disorder caused by the germ-line mutations of DNA mismatch repair (MMR) genes, especially hMLH1 and hMSH2.
Germline mutations in two human mismatch repair (MMR) genes, hMSH2 and hMLH1, appear to account for approximately 70% of the common cancer susceptibility syndrome hereditary nonpolyposis colorectal cancer (HNPCC).
Mutations in DNA mismatch repair (MMR) genes in hereditary non-polyposis colon cancer (HNPCC) patients revealed the importance of MMR deficiency as a risk for carcinogenesis.
To investigate the frequency of germline alterations of the DNA MMR genes hMLH1 and hMSH2 among African Americans affected by HNPCC and early-age onset colorectal cancer.
Hereditary nonpolyposis colorectal cancer (HNPCC), an inherited cancer predisposition syndrome, has been associated with germline mutations in DNA mismatch repair (MMR) genes.
Mutations affecting human mismatch repair (MMR) genes (MLH1, MSH2, PMS1, PMS2, and MSH6) cause tumour predisposition in hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, and an association has been demonstrated with the replication error (RER) phenotype in most colorectal and some extracolonic neoplasms.
To evaluate the respective involvement of the various MMR genes in typical and incomplete HNPCC syndromes, we have performed an analysis of the hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in a large series of French kindreds (n=75) with colorectal tumors and/or aggregation of extracolonic cancers belonging to the HNPCC spectrum.
Germline mutations of MMR genes have rarely been found in families that have HNPCC or suspected HNPCC and that do not show microsatellite instability (MSI-low phenotype).
Lynch syndrome displays many curious features that cannot be accounted for by the prevailing concepts of carcinogenesis and genetics: (1) CRCs occur preferentially in the right side of the colon, whereas the majority of sporadic cases develop in the left colon; (2) the increased risk of CRC is not associated with an increased incidence of adenomatous polyps, which are necessary precancerous lesions in the development of common CRCs; (3) the tumor spectrum in Lynch syndrome is restricted to the colon and some extracolonic sites, whereas the responsible MMR genes are ubiquitously expressed; (4) the tumor risk, which is negligible during childhood, becomes significant during adulthood at the age of 25 and thereafter remains essentially constant throughout the ages.
Significant reduction in cancer morbidity and mortality can be accomplished by appropriate clinical cancer screening of HNPCC patients with mutations in mismatch repair (MMR) genes.