Microsatellite instability: new aspects in the carcinogenesis of colorectal carcinoma.
Very recently a new molecular mechanism in the tumorigenesis of colorectal carcinoma has been described which is closely linked to hereditary non-polyposis colonic cancer (HNPCC). Ubiquitous changes in the length of simple repetitive DNA sequences between constitutional and tumour DNA occur in about 90% of cases of HNPCC and in about 15% of cases of non-familial, sporadic colorectal carcinoma. Such microsatellite instabilities have been shown to be the phenotypical marker of mutations in the human homologues of prokaryotic mismatch repair genes (MutS, MutL, MutH). These data provide crucial new tools in the detection of patients 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 of mutations in genomic stability genes leading to an increased cellular mutation rate ("mutator phenotype") and thus to cancer.
Rüschoff
J
J
Institute of Pathology, University of Regensburg, Germany.
Bocker
T
T
Schlegel
J
J
Stumm
G
G
Hofstaedter
F
F
D002273:Carcinogens / Q000494:pharmacology; D002277:Carcinoma / Q000151:congenital / Q000209:etiology* / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000151:congenital / Q000209:etiology* / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D004276:DNA, Satellite / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male
D002273:Carcinogens; D004276:DNA, Satellite