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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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).
In the wake of the discoveries that hereditary nonpolyposis colorectal cancer (HNPCC) and other human cancers are associated with mutations in MMR genes, intensive efforts are under way to elucidate the biochemical functions of mammalian MutS and MutL homologs, and the consequences of defects in these genes.
Hereditary nonpolyposis colorectal cancer (HNPCC), an inherited cancer predisposition syndrome, has been associated with germline mutations in DNA mismatch repair (MMR) genes.
In the past five years, five MMR genes could be identified as the site of germline mutations associated with a HNPCC syndrome (MSH2, MLH1, PMS1, PMS2, and MSH6).
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).