Geoffrey R. Oxnard, MD, Vincent A. Miller, MD, Mark E

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Screening for Germline EGFR T790M Mutations Through Lung Cancer Genotyping Geoffrey R. Oxnard, MD, Vincent A. Miller, MD, Mark E. Robson, MD, Christopher G. Azzoli, MD, William Pao, MD, PhD, Marc Ladanyi, MD, Maria E. Arcila, MD Journal of Thoracic Oncology Volume 7, Issue 6, Pages 1049-1052 (June 2012) DOI: 10.1097/JTO.0b013e318250ed9d Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 A case of germline T790M associated with indolent lung cancer growth. A, A germline T790M mutation was found in one patient who presented with multifocal adenocarcinoma involving the lung. Over 4 years, the patient's lung nodules displayed minimal growth, consistent with the indolent phenotype described in other lung cancers carrying the T790M mutation.11 B, Rebiopsy of the tumor shown (after observation only) identified an EGFR L858R mutation and a pretreatment T790M mutation (left). The mutant T790M peak (red) was of equal proportion to the wild-type allele (blue), consistent with the possibility of a germline mutation. After referral to clinical genetics, sequencing of peripheral white blood cell DNA (right) confirmed the germline status of the T790M mutation. Journal of Thoracic Oncology 2012 7, 1049-1052DOI: (10.1097/JTO.0b013e318250ed9d) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 A possible new strategy for the identification of “at risk” probands before referral for germline testing. Traditionally, clinical characteristics such as young age, a family history of cancer, or multiple primary cancers have been used to identify patients at risk of carrying germline mutations (left). For some cancers, such as colorectal cancer, suspicion for Lynch syndrome leads first to molecular testing (staining for mismatch repair proteins) before germline testing (middle). We propose that, for lung cancer, merely the presence of pretreatment T790M on EGFR genotyping performed for treatment planning could be sufficient to lead to germline testing (right). Journal of Thoracic Oncology 2012 7, 1049-1052DOI: (10.1097/JTO.0b013e318250ed9d) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions