Abstract 2219: Analysis of gene landscape of small cell lung cancer of Chinese through next-generation sequencing

Abstract

Abstract Background: As the more malignant subtype of lung cancer, small cell lung cancer (SCLC) displayed more aggressive and worse prognosis. Standard treatments have rarely changed in decades, therefore, in recent years, there have been attempts to explore targeted therapy and even immunotherapy. However, SCLC has more challenging targets. It was reported that almost 100% of SCLC has p53 and Rb mutations, and also has functional changes in Myc. Here we report some data about gene mutation of SCLC of Chinese patients. Methods: Tumor samples of 410 SCLC patients were consecutively collected in China from July 2018 to May 2020, next generation sequencing (NGS) was performed to detect gene mutation, and tumor mutational burden (TMB) measured by a 733 gene panel. PD-L1 expression detected by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. TPS was arranged into the following intervals: strong positive ≥50%, moderate positive ≥5% and <50%, weak positive ≥1% and <5%, and negative <1%. All these were performed by 3D Medicines, a laboratory accredited by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). Results: NGS results showed that the top gene mutation in these 410 Chinese SCLC patients were TP53 (88.0%,361/410), RB1(63.9%,262/410), BRCA1/2(34.0%,139/410), LRP1B(28.3%,116/410), FAM135B(24.1%,99/410), PIK3CA(23.9%,98/410), CYP2D6(21.0%,86/410), POLA1(20.2%,83/410), NTRK1(19.5%,80/410), MSH2(19.3%,79/410), ATM(19.3%,79/410), AKT2(18.8%,77/410), VEGFA(18.8%,77/410). Furthermore, 159 samples available for TMB analysis, and results showed that the average TMB level was 11.7 mutants/Mb, and 49.7%(79/159) were higher than 10 mutants/Mb, and 50.3%(80/159) were under 10mutants/Mb. In addition, 167 samples available for PD-L1 analysis, and results showed that 86.8% (145/167) with PD-L1 negative, 7.8(13/167) moderate positive, none with PD-L1 strong positive. Conclusion: Chinese patients with SCLC have rich spectrum of gene mutations, it suggests that targeted therapy should also have certain potential. In addition, about half of SCLCs have a TMB level above 10mutants/Mb, and immunotherapy should been considered more in the future treatment for Chinese SCLC patients. Citation Format: Jing Zhang, Hushan Zhang, Feng Ling, Yuanhan Wang, Long Li, Song Yang. Analysis of gene landscape of small cell lung cancer of Chinese through next-generation sequencing [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 2219.