Hereditary Lung Cancer Syndrome Targets Never Smokers with Germline EGFR Gene T790M Mutations

EGFR T790M Mutation in TKI-Naïve Clinical Samples: Frequency, Tissue Mosaicism, Predictive Value and Awareness on Artifacts

“…Indeed, no instances of the inherited T790M allele was revealed in 920 NSCLC patients analyzed. This does not contradict prior reports, given that only a few EGFR T790M heterozygous mutation carriers are described in the literature and considering the existence of ethnic genetic variations for the majority of known hereditary diseases [11,12]. In agreement with many previous studies, we also demonstrated that in a small proportion of treatment-naïve NSCLC cases, the EGFR T790M allele is present in the majority of tumor cells as a somatic mutation.…”

“…EGFR T790M is occasionally detected in germ-line DNA of lung cancer patients, although its actual contribution to NSCLC morbidity remains insufficiently studied [11,12]. There are data suggesting that EGFR T790M mutations occur in a subset of treatment-naïve NSCLC [13,14,15,16,17,18].…”

Germline T790M mutation of the epidermal growth factor receptor (EGFR) in a case of multifocal adenocarcinoma of the lung without exposure to Tyrosine Kinase Inhibitors (TKI): A Case Report

“…In 2014, Gazdar, et al reported somatic and germline T790M mutations in a 29 year-old female who developed NSCLC. Eight of seventeen family members tested positive for the mutation, and four of the eight developed NSCLC [1]. Our case expands the clinical spectrum of the germline EGFR T790M mutation syndrome in that our patient has multiple slow growing lung cancers (presumably bilateral) and an adenoma in the ampulla of Vater without any cancerous transformation to date.…”

“…Germline T790M mutations have been reported in patients with hereditary non-small cell lung cancer (NSCLC) [1][2][3][4]. While somatic mutations of the TKI binding domain of EGFR have been regularly reported in patients with acquired resistance to TKI therapy [5][6][7][8], the presence of the T790M mutation in this patient, who had never been exposed to a TKI, led to the diagnosis of a germline T790M mutation based upon the Guardant360 cell-free DNA (cfDNA) assay.…”

Non–Small Cell Lung Cancer, Version 6.2015

“…41,42 In these families, because T790M is, by definition, present in all cells in the cancer (and in the host), first-or second-generation TKIs have little efficacy. [34][35][36][37][38][39][40]43 Approximately 2% to 7% of patients with NSCLC have ALK gene rearrangements. is the most common fusion partner with ALK, leading to at least 13 different variants, but other fusion partners with ALK have been reported.…”