99P Landscape of homologous recombination repair gene mutations in different molecular subtypes of NSCLC

Lung cancer is one of the malignant tumors with high morbidity and mortality in world. PARP inhibitors have become a new line therapy The mechanism efficacy been well studied some cancers, especially homologous recombination (HR)-deficient ovarian cancer, several cell experiments shown that HR-deficient lung cancers are sensitive to inhibitor. Meanwhile, HHR gene potential biomarker for immunotherapy. Herein, we evaluated characteristics HRR related mutations Chinese patients adenocarcinoma (LUAD) or squamous carcinoma (LUSC). Tumor specimens from 748 NSCLC were analyzed by DNA based NGS 1021 panel this study. We 36 genes, including CHEK1/2, BRCA1/2, BRIP1, CDK12, ATM/ATR, FANCA/C/D2/E/F/G/L/M, MRE11A, NBN, RAD50/51/52, RAD51B/C/D et al. 666 746 LUAD 82 LUSC. proportions was 32.28% (215/666) LUSC 41.5% (34/82). top 5 mutated genes TAM (35/666, 5.26%), FANCM (33/666, 4.95%), CDK12 (21/666, 3.15%), BRCA2 ATR (18/666, 2.70%). In LUSC, (10/82, 12.2%), (6/82, 7.32%), FANCA (5/82, 6.10%), 6.10%). Interestingly, BRCA1 mutation not found There significant difference frequency five between (P=0.00034), CHEK2 (P=0.03521), FANCG (P=0.0009), BLM (P=0.02572), FAM175A. (P=0.03012). proportion tumor mutational burden-high (TMB-H) (≥10 mut/Mb) significantly higher mutant than wild-type (LUAD: 36.84% vs 8.82%，P<0.0001, LUSC: 75.86% 32.08%，P<0.0001). terms mutations, report different landscape. Mutations may serve as ICIs which also needs more trials verify.