APC gene mutations in the mutation cluster region are rare in esophageal cancers

Gastroenterology. 1994 Dec;107(6):1759-63. doi: 10.1016/0016-5085(94)90818-4.


Background/aims: The molecular pathogenesis of esophageal cancers is not completely understood. Frequent allelic losses occur on chromosome 5q, suggesting the presence of a tumor-suppressor gene that is important in esophageal tumorigenesis. Because the APC gene is located on chromosome 5q, we sought to determine its involvement as a candidate tumor-suppressor gene in esophageal carcinogenesis.

Methods: Thirty-five esophageal squamous cell carcinomas and 18 adenocarcinomas were collected with corresponding normal gastric mucosae. A region of APC spanning codons 686-1693 and including most reported mutations was screened for truncating mutations using an in vitro synthesized protein assay. Single-strand conformation polymorphism analysis was also used to examine APC codons 764-842 and codons 1032-1310 for missense and nonsense mutations.

Results: One squamous cell carcinoma and one adenocarcinoma each contained a truncating mutation within the mutation cluster region of APC.

Conclusions: The discovery of two truncating mutations identifies APC as a gene involved in a subset of esophageal carcinomas. The low rate of APC mutation observed here, coupled with the high reported rate of loss of heterozygosity on chromosome 5q, suggests the possibility that a gene or genes on chromosome 5q distinct from APC may be the target(s) of allelic deletion in most esophageal tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Base Sequence
  • Carcinoma, Squamous Cell / genetics
  • Chromosomes, Human, Pair 5
  • DNA Mutational Analysis
  • Esophageal Neoplasms / genetics*
  • Genes, APC / genetics*
  • Humans
  • Molecular Sequence Data
  • Multigene Family / genetics*
  • Mutation*
  • Polymorphism, Single-Stranded Conformational