Detailed analysis of genetic alterations in colorectal tumors from patients with and without familial adenomatous polyposis (FAP).
To examine early genetic events during colorectal carcinogenesis, we searched for genetic alterations in 75 adenomas from seven patients with 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 genes, 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 regardless of differences in size or histopathological classification. On the other hand, K-ras mutation was very rare in small adenomas where dysplasia 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 second '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 adenoma.
Ichii
S
S
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Takeda
S
S
Horii
A
A
Nakatsuru
S
S
Miyoshi
Y
Y
Emi
M
M
Fujiwara
Y
Y
Koyama
K
K
Furuyama
J
J
Utsunomiya
J
J
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D001483:Base Sequence; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000235:genetics*; D017491:Genes, APC; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
D009838:Oligodeoxyribonucleotides; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)