EGFR-T790M is a rare lung cancer susceptibility allele with enhanced kinase activity. Cancer Res 2007 May 15;67(10):4665-70
Date
05/19/2007Pubmed ID
17510392Pubmed Central ID
PMC3460269DOI
10.1158/0008-5472.CAN-07-0217Scopus ID
2-s2.0-34250329445 (requires institutional sign-in at Scopus site) 89 CitationsAbstract
The use of tyrosine kinase inhibitors (TKI) has yielded great success in treatment of lung adenocarcinomas. However, patients who develop resistance to TKI treatment often acquire a somatic resistance mutation (T790M) located in the catalytic cleft of the epidermal growth factor receptor (EGFR) enzyme. Recently, a report describing EGFR-T790M as a germ-line mutation suggested that this mutation may be associated with inherited susceptibility to lung cancer. Contrary to previous reports, our analysis indicates that the T790M mutation confers increased Y992 and Y1068 phosphorylation levels. In a human bronchial epithelial cell line, overexpression of EGFR-T790M displayed a growth advantage over wild-type (WT) EGFR. We also screened 237 lung cancer family probands, in addition to 45 bronchoalveolar tumors, and found that none of them contained the EGFR-T790M mutation. Our observations show that EGFR-T790M provides a proliferative advantage with respect to WT EGFR and suggest that the enhanced kinase activity of this mutant is the basis for rare cases of inherited susceptibility to lung cancer.
Author List
Vikis H, Sato M, James M, Wang D, Wang Y, Wang M, Jia D, Liu Y, Bailey-Wilson JE, Amos CI, Pinney SM, Petersen GM, de Andrade M, Yang P, Wiest JS, Fain PR, Schwartz AG, Gazdar A, Gaba C, Rothschild H, Mandal D, Kupert E, Seminara D, Viswanathan A, Govindan R, Minna J, Anderson MW, You MMESH terms used to index this publication - Major topics in bold
AllelesAnimals
COS Cells
DNA, Neoplasm
ErbB Receptors
Genes, erbB-1
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Lung Neoplasms
Pedigree
Phosphorylation
