Using next-generation sequencing for RET fusion detection in Chinese cancer patients.

Abstract

e20516 Background: Approval Selpercatinib of FDA for lung and thyroid cancer patients harboured RET mutations or fusions attracts the investigation RET fusion partners and their ability for RET‐based targeted therapy. Here, we presented a genomic characteristics of RET fusion in six cancer type among 24,087 Chinese cancer patients. Methods: Tumor samples (including tissues, formalin-fixed paraffin-embedded or plasma) obtained from patients between March 2021 and February 2023 were used for RET fusion detection. Customed probes were designed to covered all exonic and intronic regions of 6, 10 and 11 for RET. GeneFuse and Delly softwares were used for analyzing RET fusion. To ensure both sensitivity and accuracy of fusion calling, RET fusions were only reported to fuse with a set of 600 cancer-related genes and require at least two individual supporting reads. Results: A total of 233 cases with RET fusion was identified among 24,087 patients with the given six cancer types including lung cancer, thyroid cancer, coloretal cancer, pancreatic cancer, oesophageal cancer and cancer of unknown primary site. A total of 6 fusion patterns were identified in the study cohort with KIF5B, CCDC6, NCOA4 and ERC1 being the most common RET fusion partners. Notably, two novel fusion partners (i.e. GOPC and VCL) were first reported in this study. RET variants frequencies were the highest in thyroid carcinoma (13/210, 6.19%), lung cancer (212/20,402; 1.04%), esophageal cancer (1/156, 0.64%), cancer of unknown primary site (2/374, 0.53%) , pancreatic cancer (1/337, 0.29%) and colorectal cancer (5/2,608, 0.19%). The results of the analysis revealed that different tumor types tend to have preferred fusion partners. For instance, KIF5B is highly specific in lung cancer, account for 72% of cases. Meanwhile, CCDC6 and NCOA4 are both enriched in thyroid cancer (both 46%). NCOA4 also present frequently in colorectal cancer, with 80% of cases displaying this partner. Conclusions: Detection of co‐occurrence of partner and RET fusions provide a guide to clinicians in deciding tumors as candidates for RET targeted therapies.