Evaluation of MLHI 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 hereditarycolorectal cancers accounting for 5 to 10% of all colon carcinoma. it is inherited in anautosomal dominant mode and caused by hereditary mutations in mismatch repair genes(mmr) chiefly mlhi and msh2. the lifetime risk of colon cancer in affected persons is80~/0. screening, prevention strategies and consequently treatment options will beimproved by understanding of the genetic basis of this disorder. the aim of this study wasto assess mutations in mlhi and msh2 genes in a subset of iranian hnpcc patients.the families that fulfill amsterdam criteria were selected as hnpcc families. genomicdna was extracted from the peripheral blood of the samples and mutations of mlh1 andmsh2 were detected by pcr-single strand conformation polymorphism (pcr-sscp)and ona sequencing techniques. hereditary mutations were found in 20 cases. of thesemutations, 14 were found in mlh1 and 6 in msh2 genes thus mlhi gene had highermutation rate than msh2. eighteen out of 20 detected mutations in our population werepreviously reported and two were novel. our results demonstrated that mutation range aswell as genes involved in hnpcc is different from one region to other and characterizingmutations could be very helpful in diagnosis of the at risk individuals.