S. Ichii et al., DETAILED ANALYSIS OF GENETIC ALTERATIONS IN COLORECTAL TUMORS FROM PATIENTS WITH AND WITHOUT FAMILIAL ADENOMATOUS POLYPOSIS (FAP), Oncogene, 8(9), 1993, pp. 2399-2405
To examine early genetic events during colorectal carcinogenesis, we s
earched for genetic alterations in 75 adenomas from seven patients wit
h familial polyposis coli (FAP) and in 64 sporadic colorectal tumors (
63 carcinomas and one adenoma). We investigated germ-line and somatic
mutations in the APC gene, somatic mutations in the K-ras and p53 gene
s, and loss of heterozygosity (LOH) on chromosome 8p21-22. Thirty-two
FAP adenomas carried detectable somatic mutations in the APC gene. The
frequency of somatic APC mutations among adenomas was the same regard
less of differences in size or histopathological classification. On th
e other hand, K-ras mutation was very rare in small adenomas where dys
plasia was mild or moderate but frequent in large adenomas with severe
dysplasia. Mutation of the p53 gene was observed in only two adenomas
and LOH on 8p22 was detected in none. These results imply that a seco
nd 'hit' in the APC gene, but not necessarily mutation in K-ras or p53
, is an important and critical event for formation of a colorectal ade
noma.