MICROSATELLITE INSTABILITY - NEW ASPECTS IN THE CARCINOGENESIS OF COLORECTAL-CARCINOMA

Very recently a new molecular mechanism in the tumorigenesis of colore ctal carcinoma has been described which is closely linked to hereditar y non-polyposis colonic cancer (HNPCC). Ubiquitous changes in the leng th of simple repetitive DNA sequences between constitutional and tumou r DNA occur in about 90% of cases of HNPCC and in about 15% of cases o f non-familial, sporadic colorectal carcinoma. Such microsatellite ins tabilities have been shown to be the phenotypical marker of mutations in the human homologues of prokaryotic mismatch repair genes (MutS, Mu tL, MutH). These data provide crucial new tools in the detection of pa tients at high risk of developing colon cancer and other HNPCC-related carcinomas. In addition, these developments provide new insights into a new, presumably primary event in oncogenesis, i.e. the occurrence o f mutations in genomic stability genes leading to an increased cellula r mutation rate (''mutator phenotype'') and thus to cancer.