title: Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR.
abstract: Somatic activating mutations in EGFR identify a subset of non-small cell lung cancer that respond to tyrosine kinase inhibitors. Acquisition of drug resistance is linked to a specific secondary somatic mutation, EGFR T790M. Here we describe a family with multiple cases of non-small cell lung cancer associated with germline transmission of this mutation. Four of six tumors analyzed showed a secondary somatic activating EGFR mutation, arising in cis with the germline EGFR mutation T790M. These observations implicate altered EGFR signaling in genetic susceptibility to lung cancer.
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, Massachusetts 02129, USA.
authors.forename: Daphne W
authors.initials: DW
authors.lastname: Bell
authors.forename: Ira
authors.initials: I
authors.lastname: Gore
authors.forename: Ross A
authors.initials: RA
authors.lastname: Okimoto
authors.forename: Nadia
authors.initials: N
authors.lastname: Godin-Heymann
authors.forename: Raffaella
authors.initials: R
authors.lastname: Sordella
authors.forename: Roseann
authors.initials: R
authors.lastname: Mulloy
authors.forename: Sreenath V
authors.initials: SV
authors.lastname: Sharma
authors.forename: Brian W
authors.initials: BW
authors.lastname: Brannigan
authors.forename: Gayatry
authors.initials: G
authors.lastname: Mohapatra
authors.forename: Jeff
authors.initials: J
authors.lastname: Settleman
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013912:Threonine / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D013912:Threonine; D008715:Methionine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases