Proapoptotic gene BAX is frequently mutated in hereditary nonpolyposis colorectal cancers but not in adenomas.

BACKGROUND & AIMS: The p53 and BAX genes have been linked to apoptosis. p53 was not frequently found to be mutated in colorectal carcinomas with a microsatellite mutator phenotype, but frame-shift mutations in a tract of eight guanines within BAX were frequently found in these carcinomas. To understand the roles of these genes in hereditary nonpolyposis colorectal cancer (HNPCC) tumorigenesis, we examined whether BAX mutations occur in adenoma and carcinoma specimens from patients with HNPCC and also determined the frequencies of p53 mutations.

METHODS

Thirteen colorectal adenomas and 24 adenocarcinomas from patients with HNPCC showing a microsatellite instability phenotype were screened by polymerase chain reaction followed by denaturing polyacrylamide gel electrophoresis and direct sequencing.

RESULTS

Two of the 13 adenomas (15.4%) and 13 of the 24 adenocarcinomas (54.2%) showed mutation patterns and were confirmed to have frame-shift mutations at the BAX repeat site by direct sequencing. For p53, only 1 of the 24 adenocarcinomas (4.2%) showed a missense mutation.

CONCLUSIONS

In HNPCC colorectal carcinomas, BAX was significantly (P = 0.024) more mutated than in adenomas. p53 was not frequently found to be mutated in these carcinomas. These data suggest that mutations in BAX, rather than mutations in p53, may contribute to the adenoma-carcinoma transition in HNPCC tumorigenesis.