EGFR Mutations Involved In Lung Cancer Pathogenesis

NEW YORK (Reuters Health) - Mutations in the gene for epidermal growth factor receptor (EGFR) or in the KRAS gene appear to play a role in the development of non-small cell lung cancers (NSCLCs), investigators observe in the March 2nd issue of the Journal of the National Cancer Institute.

Previous reports have linked EGFR and KRAS mutations with the response to tyrosine kinase inhibitors, such as gefitinib (Iressa) or erlotinib (Tarceva) (see Reuters Health reports February 23, 2005 and January 26, 2005). However, it was unclear if mutations in these genes actually affected the development of lung cancer.

To investigate, Dr. Adi F. Gazdar, from the University of Texas Southwestern Medical Center, Dallas, and colleagues tested 617 NSCLCs, 524 normal lung samples, 36 neuroendocrine lung tumors and 243 other epithelial cancers for mutations in the tyrosine kinase domain of EGFR. In addition, the authors also evaluated the KRAS gene.

Twenty-one percent of NSCLCs harbored an EGFR mutation, whereas such mutations were absent in the other samples tested. The mutation types included in-frame deletions, missense mutations, and in-frame duplications/insertions.

Predictors of EGFR mutations included having never smoked, adenocarcinoma histology, East Asian ethnicity, and being female (p < 0.001 for all). By contrast, age at diagnosis, clinical stage, bronchioloalveolar histologic features, or overall survival were not associated with EGFR mutations.

Eight percent of NSCLCs had KRAS mutations. However, these and EGFR mutations did not co-exist, the researchers point out.

In a related editorial, Dr. William R. Sellers, from Harvard Medical School in Boston, and Dr. Matthew Meyerson, from the Massachusetts Institute of Technology in Cambridge, comment that discovery of these mutations "points out the need for a comprehensive global view of the genomes of human cancers."

Source: J Natl Cancer Inst 2005;97:326-327,339-346. [ Google search on this article ]

MeSH Headings: Membrane Proteins : Receptors, Cell Surface : Receptor, Epidermal Growth Factor : Receptors, Gastrointestinal Hormone : Gene Deletion : Receptors, Growth Factor : Receptors, Peptide