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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / enzymology
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Carcinoma, Non-Small-Cell Lung / genetics*
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Drug Resistance, Neoplasm / genetics*
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ErbB Receptors / genetics*
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Female
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Genetic Predisposition to Disease*
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Germ-Line Mutation*
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Humans
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Lung Neoplasms / drug therapy
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Lung Neoplasms / enzymology
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Lung Neoplasms / genetics*
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Male
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Methionine / genetics
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Middle Aged
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Pedigree
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Threonine / genetics
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Threonine
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Methionine
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ErbB Receptors
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Protein-Tyrosine Kinases