Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR |
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Authors: | Bell Daphne W Gore Ira Okimoto Ross A Godin-Heymann Nadia Sordella Raffaella Mulloy Roseann Sharma Sreenath V Brannigan Brian W Mohapatra Gayatry Settleman Jeff Haber Daniel A |
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Institution: | Massachusetts General Hospital Cancer Center, Harvard Medical School, 13th Street, Charlestown, Massachusetts 02129, USA. |
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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. |
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