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.