Abstract 2215: Landscape of RET fusion identified by next-generation sequencing in a Chinese multi-cancer retrospective analysis

Abstract Background: Fusion of RET with several partner genes has been detected in papillary thyroid, lung, colorectal, pancreatic and breast cancers. FDA has approved Retevmo (Selpercatinib) for lung and thyroid cancers with RET gene mutations or fusions. Here we focused on the prevalence of RET fusions in a Multi-cancer cohort (besides lung and thyroid cancers) for patients (pts) whom might benefit from RET inhibitors in clinical development. Methods: Genomic profiling was performed on 12,888 lung cancer pts, 2,848 colorectal cancer pts, 1,785 liver cancer pts, 1,169 Gastric cancer pts and 232 thyroid cancer pts from Jan. 2017 to Dec. 2019 using next-generation sequencing (NGS), which covers all exons of RET and specific intron 7-11 containing the break points of fusions. The fusion patterns of RET were analyzed. Results: A total of 165 RET fusions were identified in approximately 0.86% (163/18,922) of this Chinese multi-cancer cohort. The RET fusion-positive rates were 1.05% (135/12,888) in lung cancer pts, 0.39% (11/2,848) in the colorectal cancer pts, 0.06% (1/1,785) in liver cancer pts, 0.09% (1/1,169) in the 1169 Gastric cancer pts and 6.03% (15/232) in the 232 thyroid cancer pts tested. The most common partners were KIF5B (62.04%) and CCDC6 (21.17%) in lung cancer, NCOA4 (45.45%) and CCDC6 (27.27%) in colorectal cancer, and CCDC6 (93.33%) and NCOA4 (6.67%) in thyroid cancer. The most frequent regions of RET fusions were intron 11 (140/165) and intron 10 (15/165). The common fusion partners detected in different cancers are variable, indicating that the same oncogene has different carcinogenic mechanisms in cancers, and the sensitivity of these fusions to RET inhibitors in different cancers needs to be further studied. Conclusions: This study revealed the molecular features of RET rearrangement in Chinese cancer pts, which might result in more effective personalized diagnoses and therapies. Citation Format: Ting Lei, Weiran Wang, Danhua Wang, Junfeng Fu, Yu Wang, Ze Wang, Zhe Fan, Zhenyang Lv, Tonghui Ma. Landscape of RET fusion identified by next-generation sequencing in a Chinese multi-cancer retrospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2215.