Abstract 5308: Genetic characterization of sarcomatoid carcinomas reveals multiple novel actionable mutations and identifiesKRASmutation as a biomarker of poor prognosis

Background: Sarcomatoid component occurs in various epithelial malignancies and is associated with an aggressive disease course and poor clinical outcome. As it is largely rare, the molecular events underlying sarcomatoid carcinomas (SCs) remain poorly characterized. Here, we performed targeted next-generation sequencing (NGS) on patients with surgically resected SCs comprising distinct tissues of origin. Methods: A total of 71 patients with pathological diagnosis of sarcomatoid carcinoma and underwent surgery were retrospectively enrolled in this study. Overall survival was defined as the time from surgery to death from any cause. Patients alive or lost to follow-up were censored. Genomic DNA from formalin-fixed paraffin-embedded samples was extracted for NGS and tumor mutation burden (TMB) analysis. Results: In general, SCs occurred more commonly in males, except those of the gallbladder. SCs of the lung and the larynx were associated with a higher proportion of smokers (p=0.0015). Alterations in TP53, RB1, TERT and KRAS were highly frequent, with KRAS mutations being a biomarker of poor prognosis (median OS = 8 vs 16 months, p=0.03). Multiple novel alterations in potentially actionable genes, including ROS1 and NTRK1 fusions and ERBB2 amplification, were detected in the extra-pulmonary cohort. A relatively high proportion (30%) of extra-pulmonary SC patients had high TMB, with a median of 5.39 mutations per Mb. Lastly, copy number variations were common in SCs, and were non-overlapping between the primary and metastatic tumors. Conclusions: Taken together, our results suggest that comprehensive genetic testing may be necessary to inform treatment options and identify prognostic biomarkers. Citation Format: Ying Ding, Yang W. Shao, Chenglong Na, Jiani C. Yin, Hongjin Hua, Ran Tao, Yue Jiang, Ran Hu, Xiao He, Chen Miao, Dongqin Zhu, Zhihong Zhang. Genetic characterization of sarcomatoid carcinomas reveals multiple novel actionable mutations and identifies KRAS mutation as a biomarker of poor prognosis [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 5308.