Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene

• Published in: Human molecular genetics 1992-07, Vol.1 (4), p.229-233
• Main Authors: Mori, Yasuo, Nagse, Hiroki, Ando, Hiroshi, Horii, Akira, Ichii, Shigetoshi, Nakatsuru, Shuichi, Aoki, Takahisa, Miki, Yoshio, Mori, Takesada, Nakamura, Yusuke
• Format: Article
• Language: English
• Subjects: Adenoma - complications; Adenoma - genetics; adenomatous polyposis coli; Adenomatous Polyposis Coli - complications; Adenomatous Polyposis Coli - genetics; Alleles; APC gene; Base Sequence; Biological and medical sciences; Carcinoma - complications; Carcinoma - genetics; colorectal carcinoma; Colorectal Neoplasms - complications; Colorectal Neoplasms - genetics; DNA Mutational Analysis; DNA, Neoplasm - genetics; Gastroenterology. Liver. Pancreas. Abdomen; genes; Genes, APC; Heterozygote; Humans; man; Medical sciences; Molecular Sequence Data; mutation; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/1.4.229

We examined somatic mutations of the adenomatous polyposis coil (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.