The genomic characteristics of RET fusion positive tumors in Chinese non-small cell lung cancer (NSCLC) patients

• DOI: 10.1007/s00432-022-03959-6
• Publication Date: 2022-02-26T17:02:43Z
• Authors: Guowu Wu; Longhua Guo; Yinfang Gu; Tanxiao Huang; Ming Liu; Xiaofang Zou; Bo Yang; Ping Huang; Chunling Wen; Lilan Yi; Wenting Liao; Dongdong Zhao; Junlin Zhu; Xiaoni Zhang; Yuanyuan Liu; Yan Yin; Shifu Chen
• Keywords: Male; 0301 basic medicine; 0303 health sciences; Lung Neoplasms; Oncogene Proteins, Fusion; Original Article – Clinical Oncology; Proto-Oncogene Proteins c-ret; East Asian People; Genomics; 3. Good health; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Humans; Female; Cell-Free Nucleic Acids

Abstract Background Approximately 1–2% of non-small cell lung cancer (NSCLC) patients harbor RET (rearranged during transfection) fusions. The oncogenic RET fusions could lead to constitutive kinase activation and oncogenesis.

Methods 1746 Chinese NSCLC patients were analyzed in this study. Tumor tissues were collected, and were formalin fixed, paraffin-embedded (FFPE) and archived. Peripheral blood (PB) samples were also collected from each patient as control. In addition, we selected 17 of them for cfDNA NGS testing and 14 tumor samples for immunohistochemistry testing using PD-L1 rabbit monoclonal antibody, clones 28-8 (Abcam, Cambridge, UK).

Results Of the 1746 NSCLC cases, RET rearrangements were identified in 25 cases (1.43%) with locally advanced or metastatic NSCLC, of which 20 (80%) were female. We found that 14 out of 25 patients had an KIF5B-RET fusion, with KIF5B exon15-RET exon12, KIF5B exon23-RET exon12, and KIF5B exon24-RET exon11 detected in 14, 3, and 1 patients, respectively. We also identified one novel RET fusion partner PLCE1 and 4 intergenic-breakpoint fusions.

Conclusion In this study, using the hybrid capture based next generation sequencing (NGS) techniques, we revealed the genomic profiling for the patients with RET fusion-positive NSCLC. To the best of our knowledge, this is the first study that exhibited the detailed breakpoints of Chinese NSCLC patients with RET rearrangement, and we found a novel new partner PLCE1. The results provided genomic information for patients with RET fusion which is significant for personalized clinical management in the era of precision medicine.