Mutations of the APC (adenomatous polyposis coli) gene.

Several investigators have reported germline mutations of the APC gene in patients with familial adenomatous polyposis (FAP) as well as somatic mutations in tumors developed in digestive organs (stomach, pancreas, colon, and rectum). Those results provide evidence that inactivation of the APC gene plays a significant role in FAP and in sporadic tumors of these tissues. APC mutations have led to some interesting observations. First, the great majority of the mutations found to date would result in truncation of the APC product. Second, almost all the mutations have occurred within the first half of the coding sequence, and somatic mutations in colorectal tumors are further clustered in a particular region called MCR (mutation cluster region). Third, most identified point mutations in the APC gene are transitions from cytosine to other nucleotides. Fourth, the location of germ-line mutations tends to correlate with the number of colorectal polyps in FAP patients. Furthermore, inactivation of both alleles of the APC gene seems to be required as an early event to develop most of adenomas and carcinomas in the colon and rectum as well as some of those in the stomach.