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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Acknowledgements
We thank K. Shannon and J. Johns for assistance with specimen acquisition. This work was supported in part by the US National Institutes of Health (D.W.B., D.A.H.), the Doris Duke Foundation (D.A.H.), the National Foundation for Cancer Research (D.A.H.) and the V Foundation (J.S.).
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Bell, D., Gore, I., Okimoto, R. et al. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 37, 1315–1316 (2005). https://doi.org/10.1038/ng1671
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DOI: https://doi.org/10.1038/ng1671
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