The molecular genetics of the hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) is reviewed. Recently, four genes (hMSH2, hMLH1, hPMS1, hPMS2) whose mutations are related to HNPCC were discovered. The products of these genes are homologues of the bacterial mismatch repair (MMR) system proteins MutS and MutL. Dysfunction of MMR system both in bacterial and human cells leads to the microsatellite instability (MI) in repetitive sequences of DNA. These sequences are also present in some tumor suppressor genes (e.g. TGF-beta RII or BAX). Therefore, the MI probably leads to the impairment of the cell cycle regulation and a carcinoma can develop from the clone of such cells with nonregulated growth.

Katedra genetiky a mikrobilogie Prírodovĕdecké fakulty Univerzity Karlovy Praha