P70.13 Different Types of ERBB3 Mutations in Chinese Non-Small Cell Lung Cancer Patients

Abstract

HER3, a member of the EGFR family of receptor tyrosine kinases coded by the ERBB3 gene, plays an important role in cancer, despite its lack of intrinsic kinase activity. As with genes coding for potential heterodimeric partners of HER3, EGFR, and HER2, oncogenic mutations of ERBB3 have been explored by several studies. The prevalence of these mutations in non-small-cell lung cancer (NSCLC) is unknown. The aim of this study is to investigate mutations and prognosis of NSCLC harboring ERBB3 mutations. A total of 1402 patients with non-small-cell lung cancer were recruited between July 2012 and December 2018. The status of ERBB3 mutations and other genes were detected by next generation sequencing. ERBB3 gene mutation rate was 1.14% (16/1402) in non-small cell lung cancer, including D297N (1 patient), L841I (1 patient), R833G (1 patient), V653I (1 patient), R81Efs*3 (1 patient), R391L (1 patient), D1155E (1 patient), G994S (1 patient), Q849R (1 patient), C246* (1 patient), R1125W (1 patient), R541Q (1 patient), P276H (1 patient), L841I (1 patient), A232V (1 patient) and C327S (1 patient), and median overall survival (OS) for these patients was 17.0 months. Among them, all patients were ERBB3 gene with co-occurring mutations. Among them, all patients were ERBB3 gene with co-occurring mutations. Briefly, patients with (n=5) or without (n=11) co-occurring EGFR mutations had a median OS of not up to now and 17.0 months respectively (P=0.90); patients with (n=13) or without (n=3) co-occurring TP53 mutations had a median OS of 17.0 months and 14.5 months respectively (P=0.88); patients with (n=5) or without (n=11) co-occurring KRAS mutations had a median OS of 3.0 months and not up to now respectively (P=0.04); patients with (n=3) or without (n=13) co-occurring BRCA2 mutations had a median OS of 17.0 months and not up to now respectively (P=0.74). KRAS accompanied mutations might play a good prognosis in ERBB3 gene mutation NSCLC. Our results show that ERBB3 mutations delineate an aggressive subtype of lung cancer for which a targeted treatment through ERBB3 inhibition might offer new opportunities.