title: Germline EGFR T790M mutation found in multiple members of a familial cohort.
abstract: Activating mutations in epidermal growth factor receptor (EGFR) are present in a subset of lung cancers, and predict sensitivity to EGFR tyrosine kinase inhibitors. Acquisition of EGFR T790M is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors and rarely is seen before treatment. Germline EGFR T790M mutations have been reported, although the penetrance and clinical significance of this mutation is unknown. We describe the identification of a patient with an EGFR T790M germline mutation and subsequent germline testing in her unaffected family members. Genetic testing revealed two additional EGFR T790M germline carriers, one of which was subsequently diagnosed with metastatic lung adenocarcinoma.
authors.affiliation: *Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine; †Department of Pathology, ‡Clinical Genetics Service, Department of Medicine, §Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York; and ‖Weill Cornell Medical College, New York, New York.
authors.forename: Helena A
authors.initials: HA
authors.lastname: Yu
authors.forename: Maria E
authors.initials: ME
authors.lastname: Arcila
authors.forename: Megan
authors.initials: M
authors.lastname: Harlan Fleischut
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Stadler
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Michael F
authors.initials: MF
authors.lastname: Berger
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D000328:Adult; D066246:ErbB Receptors / Q000235:genetics*; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
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