Abstract 1317: RET aberrations in Chinese solid tumor patients: Next-generation sequencing of 10194 patients

Abstract

Abstract Purpose: RET is an emerging oncogenic target showing promise in phase I/II clinical trials, but the comprehensive genomic landscape of RET aberrations across multiple cancers has had limited exploration. Experimental Design: We interrogated the molecular portfolio of 10194 patients with diverse cancers for the presence of RET aberrations using targeted next-generation sequencing (NGS) of 450 genes panel (OrigiMed, Shanghai). Results: Among various cancer types, RET aberrations were identified in 234 cases (2.3%, 234/10 194), with mutations being the most common alteration (62.4%, 146/234), followed by fusions (19.2%, 45/234), amplifications (13.2%, 31/234), and rearrangements (5.1%, 12/234). The proportion of RET mutations in papillary thyroid carcinoma, lung adenocarcinoma, colorectal adenocarcinoma, small cell lung cancer, and other subtypes was 28.6%, 4.2%, 3.6%, 3.0%, and 16.5% respectively. Most patients had coexisting aberrations in addition to RET anomalies (73.5%, 172/234), with the most common being in TP53-associated genes (40.2%, 94/234), the Wnt signaling pathway (39.3%, 92/234), the HR signaling pathway (19.2%, 45/234), the PI3K signaling pathway (17.5%, 41/234), and MAPK effectors (16.2%, 38/234). All 172 patients harboring coexisting aberrations had distinct genomic portfolios. Conclusions: This study revealed RET aberrations in 2.3% of Chinese solid tumor patients. RET aberrations were detected more in papillary thyroid carcinoma, lung adenocarcinoma, colorectal adenocarcinoma, and small cell lung cancer. Most cases harbored actionable, albeit distinct, coexisting alterations, all of which may potentially contribute to more effective treatment options in the future. Citation Format: Chengzhi Zhou, Junhang Zhang, Zhuojian Shen, Hongbiao Wang, Yun Li, Minghui Wang, Qin Fu, Lin Zhang, Angen Liu. RET aberrations in Chinese solid tumor patients: Next-generation sequencing of 10194 patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1317.