Abstract 5885: The impact of genomic mutational status and correlation with tumor mutation burden in non-small cell lung cancer of Xuanwei, Yunnan Province, China
Authors: Yinqiang Liu, Jin Liang, Juan Zhao, Shuirong Zhang, Shiyue Zhang, Yunfei Shi, Ruoshan Huang, Xiaojie Wang
Journal: Cancer Research (2020)

Abstract Background: Xuanwei County in Yunnan Province is one of the regions with the highest lung cancer mortality rates in China, the mortality rate in female lung cancer ranks first in China. Our previous study identified a higher mutation frequency of KRAS (25%) and EGFR uncommon mutations (56.4%) in a Xuanwei cohort compared to a large cohort of Chinese patients(pts) with non-small cell lung cancer (NSCLC) (n=1200). Tumor mutation burden (TMB) is a predictive biomarker for immune checkpoint inhibitors in NSCLC. The aim of this study was to explore gene mutations and the correlation with TMB in Xuanwei NSCLC pts. Materials and Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor samples and matched blood samples of 111 Xuanwei NSCLC pts were collected for 450 cancer gene next-generation sequencing (NGS) targeted panel assay. Genomic alterations (GAs), including single base substitution, short and long insertion/deletions, copy number variations, gene fusions, and rearrangements, and TMB values were assessed with a mean coverage of 1000X. Results: Tumor samples were lung adenocarcinoma (LUAD) (n=99, 89.2%), lung squamous cell carcinoma (LUSC) (n=6, 5.4%), or others (n=6, 5.4%). The cohort included 58 males (52.3%) and 53 females (47.7%) with a median age of 54 years (range 36-78). In total, 73.8% of the pts had one or more actionable GAs. The most common were TP53 (51%), EGFR (49%), KRAS (28%), LRP1B (26%), SPTA1 (23%), NF1 (18%), MED12 (14%), RBM10 (14%), and KMT2C (13%). TMB high (TMB-H) (≥10 muts/Mb) was seen in 58.5% (65/111) of the Xuanwei cohort compared with 29.4% of the Chinese cohort(P &amp;lt;0.001), and the Xuanwei cohort had a higher median TMB than the Chinese cohort (13.1 vs 4.6 muts/Mb, respectively, P &amp;lt;0.001). A higher TMB was associated with higher age, and TMB was higher in males and current/former smokers. Genomic alterations associated with TMB were analysised. Among the common actionable mutations. KRAS mutation cases had a higher median TMB than KRAS wildtype (21.1 vs 9.6 muts/Mb, respectively, P &amp;lt;0.01). TMB-H was seen in 80.6% (25/31) of the Xuanwei KRAS mutation cohort. KRAS G12C (61.3%, 19/31) was the most common mutation and these cases showed lower TMB than non-KRAS G12C cases (P&amp;lt;0.05). EGFR mutations were significantly adversely correlated with TMB (P &amp;lt;0.001). Tumors with the common mutations in EGFR showed significantly lower TMB than those with the uncommon mutations in EGFR (P &amp;lt;0.01). TP53, LRP1B, SPTA1, NF1, and KMT2C mutations frequently occurred in NSCLC pts and were significantly positively correlated with TMB(p&amp;lt;0.001, p&amp;lt;0.001, p&amp;lt;0.001, p&amp;lt;0.001, and p&amp;lt;0.001, respectively). Conclusions: The Xuanwei NSCLC cohort had a higher median TMB than the Chinese NSCLC cohort. KRAS, TP53, LRP1B, SPTA1, NF1, and KMT2C mutations positively correlated with TMB while EGFR mutations were significantly adversely correlated with TMB. NGS revealed potential immunotherapy biomarkers for Xuanwei NSCLC pts. Citation Format: Yinqiang Liu, Jin Liang, Juan Zhao, Shuirong Zhang, Shiyue Zhang, Yunfei Shi, Ruoshan Huang, Xiaojie Wang. The impact of genomic mutational status and correlation with tumor mutation burden in non-small cell lung cancer of Xuanwei, Yunnan Province, China [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5885.