P1.12-10 The Genomic Profiles of Small Cell Lung Cancer in East Asian

Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with poor survival, which is initially effective treated by chemotherapy and relapses rapidly. Comprehensive genomic analysis of SCLC contribute to the understanding of drug resistance mechanisms and discerning patients who respond to treatments, especially immunotherapy that has been proved to be efficient in SCLCs harboring high tumor mutational burden (TMB). This study was initiated to investigate the genomic profiles of SCLC in Chinese. SCLC specimens were obtained by surgery or biopsy from 64 patients. Whole-exome sequencing (WES) was performed on tumor samples without paired PBMCs. Alterations were confirmed with VAF between 5% and 90%, subsequently filtered by mutated genes above 5% in J.Geroge’s and LY. Jiang’s researches. Tumor mutational burden was calculated by the number of non-synonymous mutations. The mutations of highly mutated driver genes in SCLC was also determined based on MH. Bailey’s study. TP53 and RB1 were the most frequently mutated genes in SCLCs, occurred in 87.5% (56/64) tumors, and furthermore related to a higher mutational burden (P = 0.0008 and 0.0274, respectively). Tumor mutational burden after filtered by highly mutated genes in SCLC was 333 non-synonymous mutations per tumor, with high mutation rates exhibited in advanced stage of SCLCs, while the smoking history did not correlate with the number of mutations. Driver genes mutation in high frequency was detected almost in all tumors (63/64), with 17.4 mutations on average (0-144). Tumors with POLE mutation tended to harbor a higher driver genes mutation rates, as well as a higher TMB. Pathway analysis using altered driver genes showed enrichment of PI3K-Akt (adj. P = 8.38e-07), MAPK (adj. P = 1.63e-05), mismatch repair (adj. P = 4.55e-05), cell cycle (adj. P= 0.0016), and Wnt (adj. P= 0.0047) signaling pathways. We did not observe significant correlation of mutations in Wnt signaling pathway with survival, though it has proved to be a mechanism of chemoresistance in SCLCs. SCLCs exhibited complex genomic features with extensive mutational burden and high numbers of altered driver genes. Various sorts of cancer-related pathways were enriched, highlighted the complicacy of SCLCs.