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.