Prevalence of MLH1/MSH2 mutations in CRC families was significantly increased by the presence of: (i) fulfilled Amsterdam criteria; (ii) four or more CRCs; or (iii) one or more endometrial cancer.
We sequenced the MLH1/MSH2 coding and promoter core regions in CRC patients diagnosed below age 40, and/or with multiple primary cancers or familial cancer clustering suggestive of HNPCC, and correlated deleterious mutations with clinical and tumour features.
We suggest that the I1307K mutation may contribute to CRC in Israeli Arabs and that inactivating mutations of MSH2 and MLH1 may not be a major cause for early onset CRC.
These results indicate that there are different oncogenic pathways in the MSI sporadic colorectal cancers with germline missense mutations in the hMSH2 gene.
In order to better understand the role of somatic and germline alterations within hMSH2 and hMLH1 in the process of colorectal tumorigenesis, we examined the entire coding regions of both of these genes in seven patients with MIN+ sporadic colorectal cancer, 19 patients with familial colorectal cancer, and 20 patients meeting the strict Amsterdam criteria for HNPCC.
Prevalence of MLH1/MSH2 mutations in CRC families was significantly increased by the presence of: (i) fulfilled Amsterdam criteria; (ii) four or more CRCs; or (iii) one or more endometrial cancer.
In order to assess the role of these genes in sporadic RER+ colorectal carcinoma, we have carried out a mutation analysis of MSH2 and MLH1 by two-dimensional (2-D) DNA electrophoresis, including heteroduplexing and separation in a denaturing gradient.
Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA.