P1.14-10 The Landscape of RET Genomic Alterations in Chinese Non-Small Cell Lung Cancer Patients

RET is known as a driver gene which accounts for 1-2% in NSCLC. Recently, RET inhibitors such as LOXO-292 and BLU-667 demonstrated promising efficacy in NSCLC and medullary thyroid cancer. The landscape of RET alterations of the Chinese NSCLC population will be explored in this study. FFPE tumor and matched blood samples of 3433 Chinese NSCLC patients were collected for performing next-generation sequencing (NGS) based targeted panel sequencing. The genomic variants including single nucleotide variations, indels, copy number alterations and gene rearrangements were analyzed. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were calculated and assessed by NGS algorithms. The patients with RET alterations, including 61 males and 57 females with a median age of 59.5 years, were identified in approximately 3.4% (118/3433) of the Chinese NSCLC cohort. In this study, 58 out of 118 (1.7%) patients, including 21 males and 37 females with a median age of 58 years, harbored RET rearrangements, which is slightly higher than the published data of MSKCC (1.2%). The partner genes of RET rearrangements were identified by NGS, including KIF5B (38/58), CCDC6 (6/58), and other genes (14/58). TP53 was the most common compound gene with RET rearrangements. Two co-existing EGFR mutations, L858R and L861Q, were identified in 2 RET rearrangement patients without previous treatments. Harbored alterations in the cell cycle pathway and in the PI3K/mTOR pathway were found in 15.5% (9/58) and 12.1% (7/58) of patients, respectively. In addition, 8 patients with RET rearrangements had no other co-occurring common cancer gene mutations. Meanwhile, 56 (1.6%) patients carried RET mutations and 5 (0.2%) patients presented RET amplifications. The median TMB of patients with RET alteration was 4.6 muts/Mb, which was exactly the same as all the 3433 patients (4.6 muts/Mb). Interestingly, patients with RET rearrangements had lower TMB (2.3 muts/Mb, 0-16.2 muts/Mb). All patients with RET alternations were microsatellite stable (MSS). This is the first study to reveal RET genomic profiling in a large Chinese NSCLC cohort. RET rearrangements were found in 1.7% of Chinese NSCLC. Besides the most common partner genes, 14 RET rearrangements (24%) with uncommon or novel partner genes were identified by NGS. TMB of the patients with RET rearrangements was relatively lower.