DNA Mismatch Repair and Hereditary Nonpolyposis Colorectal Cancer

Abstract

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disorder which is characterized by the absence of a premalignant phenotype. Until recently, the only method to identify persons with a predisposition to develop colorectal cancer was by rigorous anamnestic questioning of their family history. The recent discovery that mutations in genes associated with mismatch repair predispose persons to the development of HNPCC has on the one hand provided a more accurate alternative to pedigree analysis but on the other is accompanied by special difficulties with respect to genetic counselling. This review focuses on what is meant by HNPCC, the current knowledge of mismatch repair, mismatch repair gene mutations, their resulting genetic phenotype, its implication in tumour development and screening alternatives for gene carriers.

Hereditary nonpolyposis colorectal cancer: causative role of a germline missense mutation in the hMLH1 gene confirmed by the independent occurrence of the same somatic mutation in tumour tissue

“…Once the HNPCC susceptibility loci had been identified, screening for germline mutations in DNA mismatch repair genes and presymptomatic diagnosis in persons at risk became possible (for reviews, see de la Chapelle and Peltomäki 1995; Marra and Boland 1995;Liu et al 1996;Scott 1997). Mutations in the hMSH2 and hMLH1 genes are responsible for disease in most HNPCC patients, although the DNA mismatch repair system includes at least four different genes (Liu et al 1996).…”