EP1.03-28 Frequency and Molecular Characteristics of BRCA1 Mutations in Non-Small Cell Lung Cancer from East Asian Patients

Abstract

Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. The aim of this study is to investigate mutations and prognosis of NSCLC harboring BRCA1 mutations. A total of 730 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of BRCA1 mutations and other genes were detected by next generation sequencing. BRCA1 gene mutation rate was 2.60% (19/730) in non-small cell lung cancer, including Y856H (3 patients), M1689T (2 patients), N909I (2 patients), G275D (2 patients), N473S (2 patients), S1217C (1 patient), M1628T (1 patient), E649* (1 patient), R1443* (1 patient), V191I (1 patient), I783V (1 patient), M669T (1 patient), and R71K (1 patient), and median overall survival (OS) for these patients was 14.0 months. Among them, all patients were BRCA1 gene with co-occurring mutations. Briefly, patients with (n=3) or without (n=16) co-occurring EGFR mutations had a median OS of 20.0 months and 13.0 months respectively (P=0.56); patients with (n=4) or without (n=15) co-occurring TP53 mutations had a median OS of 20.0 months and 19.5 months respectively (P=0.82); patients with (n=4) or without (n=15) co-occurring PIK3CA mutations had a median OS of not up to now and 13.5 months respectively (P=0.36); patients with (n=5) or without (n=14) co-occurring CDKN2A mutations had a median OS of not up to now months and 13.5 months respectively (P=0.28). Our data reveal BRCA1 mutations represent a distinct subset of NSCLC. NGS might be useful for evaluation of BRCA1 unclassified variants. Our results show that BRCA1 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through PARP inhibition might offer new opportunities.