Abstract 206: The landscape of oncogenic gene fusions in Chinese colorectal cancer patients

Abstract

Abstract Background: Oncogenic gene fusions have been reported in patients with colorectal cancer (CRC) as promising actionable targets, but recognition of rare molecular subgroups is a challenge for precision oncology. We aimed to comprehensively characterize the clinical, pathological, and molecular landscape of Chinese CRC patients with oncogenic gene fusions. Methods: A total of 1226 patients with CRC underwent genomic testing between Aug. 2017 and Sep. 2019 using a tissue-based next-generation sequencing (NGS) assay. All the coding exons of 450 cancer-related genes and selected introns were captured by the custom hybridization capture panel. Microsatellite instability (MSI) and tumor mutational burden (TMB) were assessed in all patients. Results: Oncogenic gene fusions were found in 1.6% (20/1226) of Chinese CRC tumors, which was higher than that in the western population (0.68%, R. Madison, ESMO 2018 Congress). The most frequently detected fusions were NTRK1 (N = 5, 25%), BRAF (N = 5, 25%), ALK (N = 3, 15%), NTRK3 (N = 2, 10%), and RET (N = 2, 10%). FGFR1, ROS1, and EGFR fusions each occurred in one patient. Compared with patients without fusions, those with fusions were older (median age 69 vs 59 years, respectively, P=0.009), had right-sided CRC (75.0% vs 27.4%, respectively, P<0.001), MSI-high (45.0% vs 8.7%, respectively, P<0.001), and a higher TMB (median TMB of 9.8 vs 5.6 muts/mb, respectively). All MSI-high patients with fusions were TMB-high with a median value of 73.5 muts/Mb (range 51.8-180.3). The most frequently co-mutated genes in fusion cases were TP53 (70%), APC (60%), KMT2D (50%), ACVR2A (45%), RNF43 (45%), and TGFBR2 (40%). KRAS, NRAS, BRAF, POLE, and mismatch repair gene mutations were all mutually exclusive with oncogenic gene fusions. One patient harboring an EGFR-SEPT14 fusion, who had been heavily treated for right colon cancer metastasis, achieved a partial response to erlotinib. Conclusions: This study revealed that oncogenic gene fusions were found in 1.6% of Chinese CRC patients by using a tissue-based NGS assay. As oncogenic gene fusions are mutually exclusive with common oncogenic mutations, using NGS to detect fusions as actionable targets or resistance mechanisms has notable implications for precision therapy. Citation Format: Zhenhai Lu, Rongfeng Song, Kunsong Li, Ying Cheng, Wenjing Wang, Weifeng Wang. The landscape of oncogenic gene fusions in Chinese colorectal cancer 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 206.