Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR.
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.
Bell
Daphne W
DW
Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, Massachusetts 02129, USA.
Gore
Ira
I
Okimoto
Ross A
RA
Godin-Heymann
Nadia
N
Sordella
Raffaella
R
Mulloy
Roseann
R
Sharma
Sreenath V
SV
Brannigan
Brian W
BW
Mohapatra
Gayatry
G
Settleman
Jeff
J
Haber
Daniel A
DA
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
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D013912:Threonine; D008715:Methionine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases