In this study, we examined the frequency of this novel mechanism for MSH2 inactivation in cases recruited through the Colon Cancer Family Registry and from the Mayo Clinic Molecular Diagnostics Laboratory.
Colon cancer tissue was assayed using immunohistochemistry for expression of hMLH1 and hMSH2, and a panel of five pairs of microsatellite primers (NR21, NR22, NR24, BAT25, and BAT26) for MSI-H analysis and additional dinucleotide markers (D17S250, D5S346, and D2S123) used for MSI-L.
The pedigree analysis suggested that the newly detected nonsense mutation in exon 7 of the hMSH2 gene might be responsible for the development of colon cancers.
Among the original 519 patients, nine (all with colon cancer in the family) were diagnosed with HNPCC at the outset-six with MLH1 and three with MSH2 mutations.
Furthermore, in human sporadic colon cancers, HIF-1alpha overexpression is statistically associated with the loss of MSH2 expression, especially when p53 is immunochemically undetectable.
Mismatch repair (hMLH1 and hMSH2) and p53 status was investigated immunohistochemically in 111 proximal colon cancers along with tumor TNM stage, grade, and extramural vascular invasion.
A prospective study of psychosocial consequences following predictive testing for inherited mutations in breast/ovarian and colon cancer susceptibility genes BRCA1, BRCA2, MLH1, and MSH2 was performed.
It is important to evaluate the effects of proposed interventions to reduce the risk of disease among carriers of a highly penetrant mutation, such as the mutations in BRCA1 and BRCA2 for breast and ovarian cancers or in APC and MLH1 or MSH2 for colon cancer.
A family history of breast/ovarian, HNPCC or colon cancer in a first degree relative was found in 40% of fallopian, 20% of biliary, 35% of pancreatic, 27% of urothelial and 20% of small bowel cancer patients.
These results suggest that testing for the MSH2*1906G>C mutation should be included in the evaluation of Ashkenazi Jewish individuals diagnosed with early-onset colon cancer.
This type of genetic instability is a key event in the malignant progression of HNPCC and a subset of sporadic colon cancers and mutation rates are particularly high at short repetitive sequences.
We screened germline mutations of mismatch repair genes hMLH1 and hMSH2 in a patient with multiple primary neoplasms (multiple stomach cancers, colon cancer and brain tumor) in a cancer clustered HNPCC family.
Members of hereditary nonpolyposis colon cancer (HNPCC) families harboring heterozygous germline mutations in the DNA mismatch repair genes hMSH2 or hMLH1 present with tumors generally two to three decades earlier than individuals with nonfamilial sporadic colon cancer.
Microsatellite instability and hMSH2 gene mutation in a triple cancer (colon cancer, endometrial cancer, ovarian cancer) patient in hereditary non-polyposis colorectal cancer (HNPCC) kindred.
We describe a case of a young woman with colon cancer with no clinical criteria of hereditary nonpolyposis colorectal cancer, whose genetic analysis showed that the tumor displayed microsatellite instability, and in whom a truncated protein in hMSH2 gene was found, which was also present in two at-risk relatives.
The present study was designed to determine the frequency of germline mutations in the hMLH1 and hMSH2 genes in 31 families suspected of having hereditary nonpolyposis colorectal cancer who do not fulfill the criteria of the International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer but in whom a genetic basis for colon cancer is strongly suspected and 45 patients with sporadic early-onset colorectal cancer who developed colorectal cancer before the age of 40 years without any family history of colorectal cancer.
We analyzed microsatellite instability, alterations of the polyadenine tract in TGF-beta RII (transforming growth factor beta type II receptor gene), and mutations of hMSH2 and hMLH1 in 32 patients with familial colorectal cancer (29 kindreds) fulfilling the clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC), defined at the 34th Annual Meeting of Japanese Society for Cancer of the Colon and Rectum (Tokushima, Japan, 1991), including five kindreds fulfilling the Amsterdam criteria.