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

Hum Mol Genet. 1992 Jul;1(4):229-33. doi: 10.1093/hmg/1.4.229.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / complications
  • Adenoma / genetics
  • Adenomatous Polyposis Coli / complications
  • Adenomatous Polyposis Coli / genetics*
  • Alleles
  • Base Sequence
  • Carcinoma / complications
  • Carcinoma / genetics
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / genetics*
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Genes, APC*
  • Heterozygote
  • Humans
  • Molecular Sequence Data


  • DNA, Neoplasm