Nature Genetics 37, 1315 - 1316 (2005)
Published online: 30 October 2005; | doi:10.1038/ng1671
Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFRDaphne W Bell1, Ira Gore2, Ross A Okimoto1, Nadia Godin-Heymann1, Raffaella Sordella1, Roseann Mulloy1, Sreenath V Sharma1, Brian W Brannigan1, Gayatry Mohapatra3, Jeff Settleman1
& Daniel A Haber11
Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, Massachusetts 02129, USA. 2
Bruno Cancer Center, St. Vincent's Hospital, Birmingham, Alabama 35205, USA. 3
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Correspondence should be addressed to Daniel A Haber haber@helix.mgh.harvard.edu 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.
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