title: Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene.
abstract: We examined somatic mutations of the adenomatous polyposis coli (APC) gene in 63 colorectal tumors (16 adenomas and 47 carcinomas) developed in familial adenomatous polyposis (FAP) and non-FAP patients. In addition to loss of heterozygosity (LOH) at the APC locus in 30 tumors, 43 other somatic mutations were detected. Twenty-one of them were point mutations; 16 nonsense and two missense mutations, and three occurred in introns at the splicing site. Twenty-two tumors had frameshift mutations due to deletion or insertion; nineteen of them were deletions of one to 31 bp and three were a 1-bp insertion. One tumor had a 1-bp deletion in an intron near the splicing site. Hence, 41 (95%) of 43 mutations resulted in truncation of the APC protein. Over 60% of the somatic mutations in the APC gene were clustered within a small region of exon 15, designated as MCR (mutation cluster region), which accounted for less than 10% of the coding region. Combining these data and the results of LOH, more than 80% of tumors (14 adenomas and 39 carcinomas) had at least one mutation in the APC gene, of which more than 60% (9 adenomas and 23 carcinomas) had two mutations. These results strongly suggest that somatic mutations of the APC gene are associated with development of a great majority of colorectal tumors.
authors.affiliation: Department of Biochemistry, Cancer Institute, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: H
authors.initials: H
authors.lastname: Nagase
authors.forename: H
authors.initials: H
authors.lastname: Ando
authors.forename: A
authors.initials: A
authors.lastname: Horii
authors.forename: S
authors.initials: S
authors.lastname: Ichii
authors.forename: S
authors.initials: S
authors.lastname: Nakatsuru
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.forename: Y
authors.initials: Y
authors.lastname: Miki
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000236:Adenoma / Q000150:complications / Q000235:genetics; D011125:Adenomatous Polyposis Coli / Q000150:complications / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D002277:Carcinoma / Q000150:complications / Q000235:genetics; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D017491:Genes, APC; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D004273:DNA, Neoplasm