POINT MUTATION OF THE C-KI-RAS PROTOONCOGENE AND THE P53 TUMOR-SUPPRESSOR GENE IN DISTAL COLONIC ADENOCARCINOMAS

One hundred and twenty-seven monochronous primary colorectal adenocarc inomas were examined for both activation of the c-Ki-ras proto-oncogen e by point mutation in codons 12 or 13 and inactivation of the p53 tum our suppressor gene by point mutation in exons four through nine. All of the carcinomas originated in the distal half of the colorectum. Act ivation of the c-Ki-ras proto-oncogene was detected in 23% (29/127) of adenocarcinomas, and p53 inactivation was detected in 63% (80/127) of adenocarcinomas. Only 16% (20/127) of cases exhibited both genetic ch anges, and no association was noted between the occurrence of these tw o changes. Individually, both ras activation and p53 inactivation were associated with a poorer patient prognosis (p=0.0009 and p=0.0159 res pectively). In a Cox regression analysis both ras activation and p53 i nactivation contributed independently towards patient mortality. These results suggest that mutations exert their effect independently of ea ch other, and that it is the cumulative mutational load that determine s a patient's prognosis.