Evaluation of MLH1 and MSH2 Gene Mutations in a Subset of Iranian Families with Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

Hereditary nonpolyposis colorectal cancer is the most common form of hereditary colorectal cancers accounting for 5 to 10% of all colon carcinoma. It is inherited in an autosomal dominant mode and caused by hereditary mutations in mismatch repair genes (MMR) chiefly MLH1 and MSH2. The lifetime risk of colon cancer in affected persons is 80%. Screening, prevention strategies and consequently treatment options will be improved by understanding of the genetic basis of this disorder. The aim of this study was to assess mutations in MLH1 and MSH2 genes in a subset of Iranian HNPCC patients. The families that fulfill Amsterdam criteria were selected as HNPCC families. Genomic DNA was extracted from the peripheral blood of the samples and mutations of MLH1 and MSH2 were detected by PCR-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing techniques. Hereditary mutations were found in 20 cases. Of these mutations, 14 were found in MLH1 and 6 in MSH2 genes thus MLH1 gene had higher mutation rate than MSH2. Eighteen out of 20 detected mutations in our population were previously reported and two were novel. Our results demonstrated that mutation range as well as genes involved in HNPCC is different from one region to other and characterizing mutations could be very helpful in diagnosis of the at risk individuals.

Hereditary nonpolyposis colorectal cancer is the most common form of hereditary colorectal cancers accounting for 5 to 10% of all colon carcinoma. It is inherited in an autosomal dominant mode and caused by hereditary mutations in mismatch repair genes (MMR) chiefly MLH1 and MSH2. The lifetime risk of colon cancer in affected persons is 80%. Screening, prevention strategies and consequently treatment options will be improved by understanding of the genetic basis of this disorder. The aim of this study was to assess mutations in MLH1 and MSH2 genes in a subset of Iranian HNPCC patients. The families that fulfill Amsterdam criteria were selected as HNPCC families. Genomic DNA was extracted from the peripheral blood of the samples and mutations of MLH1 and MSH2 were detected by PCR-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing techniques. Hereditary mutations were found in 20 cases. Of these mutations, 14 were found in MLH1 and 6 in MSH2 genes thus MLH1 gene had higher mutation rate than MSH2. Eighteen out of 20 detected mutations in our population were previously reported and two were novel. Our results demonstrated that mutation range as well as genes involved in HNPCC is different from one region to other and characterizing mutations could be very helpful in diagnosis of the at risk individuals.