APC mutations are infrequent but present in human lung cancer

Cancer Lett. 2004 Apr 30;207(2):197-203. doi: 10.1016/j.canlet.2003.10.020.

Abstract

Recent studies have revealed the presence of beta-catenin mutations in a small subset of human and rat lung carcinomas, suggesting the involvement of the Wnt pathway in pulmonary carcinogenesis. LOH on chromosome 5q (APC locus) is frequent in lung cancer, but previous studies have found no adenomatous polyposis coli (APC) mutations. In this study, we screened 114 human lung cancer specimens for alterations in the mutation cluster region of the APC gene and in exon 3 of the beta-catenin gene. SSCP followed by direct DNA sequencing revealed APC mutations in 2/44 (5%) squamous cell carcinomas, a 2-bp deletion in codon 1465 (AGT-->A), and a GAA-->CAA (Glu-->Gln) mutation at codon 1317. One of 32 (3%) small cell lung carcinomas contained a GAA-->AAA (Glu-->Lys) mutation at codon 1284. Two cases with an APC mutation showed focal nuclear beta-catenin staining. These results suggest that disruption of the Wnt pathway through APC mutations is infrequent, but may be involved in the pathogenesis of a small subset of human lung carcinomas.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenomatous Polyposis Coli / genetics
  • Adenomatous Polyposis Coli / metabolism
  • Adenomatous Polyposis Coli / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Small Cell / genetics
  • Carcinoma, Small Cell / metabolism
  • Carcinoma, Small Cell / pathology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Genes, APC / physiology*
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Middle Aged
  • Mutation / genetics*
  • Polymorphism, Single-Stranded Conformational
  • Proto-Oncogene Proteins / genetics
  • Sequence Deletion
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Wnt Proteins
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin