Mutations of the epidermal growth factor receptor gene in gastrointestinal tract tumor cell lines

Abstract

The epidermal growth factor receptor (EGFR) is commonly overexpressed in many human tumors including gastrointestinal tract tumors. Gefitinib is a selective inhibitor of EGFR tyrosine kinase, and blocks several signal transduction pathways including those involved in tumor cell proliferation, angiogenesis and metastasis. Recent mutational and biological studies have suggested that mutations in the tyrosine kinase domain of the EGFR gene are well correlated with the response to gefitinib, and that these mutations are frequently observed in non-small cell lung cancers affecting women, East Asians and nonsmokers. This led us to speculate that EGFR gene mutations may occur frequently in gastrointestinal tract carcinomas (GITCs) because over-expression is observed in these tumor types. To investigate EGFR mutations in GICTs, we studied 11 esophageal, 6 gastric, and 12 colorectal cancer cell lines. We found a missense mutation in a gastric cancer cell line, and 10 single nucleotide polymorphisms. The occurrence of rare mutations in the tyrosine kinase domain of the EGFR gene suggests that gefitinib is unlikely to be reliable as single-drug therapy for GITCs.