Abstract 173P
Background
The emergence of immunotherapy brings new opportunities for the treatment of LSCC. The present study aims to analyze the genomic characteristics of Chinese lung squamous cell carcinoma (LSCC) and to investigate its correlation with tissue tumor mutational burden (tTMB) and PD-L1 expression.
Methods
101 LSCC tissue samples were collected and detected by OncoDrug-Seq 603-gene panel assay through next-generation sequencing (NGS), and PD-L1 expression detected by FDA-approved 22C3 antibody.
Results
The median age of 101 patients was 68 years with the range 33 to 88 years. The mean tTMB and the median tTMB were 10.36 mutations and 9.0 mut/Mb, respectively, which parallelled to the results from TCGA (mean tTMB, 8.1 mut/Mb; median tTMB, 8.4 mut/Mb), and the CHOICE (mean tTMB, 11.8 mut/Mb) study. Positive PD-L1 expressions (CPS≥1%) were identified in 44%, high expressions of PD-L1 (CPS≥50%) were 17%. Both high tTMB and positive PD-L1 expression are independent. We identified eight genes with a somatic mutation frequency over 15% in all cases: TP53(66%), KMT2D (36%), FAT3(36%), PDE4DIP (30%), KMT2C(24%), FAT1(23%), TET1(19%), and CDKN2A(18%), respectively. Copy number variations (CNVs) were detected among 8 genes: CDKN2B, CDKN2A, FGF4, FGF19, FGF3, PTEN, EGFR, CCND1, FGFR1, ERBB2, MET. Loss of heterozygosity (LOH) was observed in CDKN2B, CDKN2A and PTEN. LSCC with LOH in CDKN2B (11%) was the most frequent event in our study. We also found 3 patients with EML4-ALK, ERBB2-GRB7, and EMBP1-BRAF fusions. Furthermore, mutations in TP53(P=0.000379) and CDKN2A(P=0.003732) were significantly associated with higher tTMB.
Conclusions
We found that mutations in TP53 and CDKN2A were significantly associated with higher tTMB in Chinese LSCC. While genetic alteration frequency had no statistical difference with PD-L1 expression level, and there was no significant correlation among gene amplification and tTMB, PD-L1 expressions. However, the combination of genomic characteristics, including mutations, tTMB, and PD-L1 expression may further assist to promote the optimization immunotherapy strategiy in Chinese LSCC populations.
Legal entity responsible for the study
Shanghai Topgen Biomedical Technology Co., Ltd.
Funding
Has not received any funding.
Disclosure
Q. Yang, C. Xia, S. Ding: Other, Personal and Institutional, Full or part-time Employment: Shanghai Topgen Biomedical Technology Co., Ltd. P. Luo: Financial Interests, Personal, Ownership Interest: Shanghai Topgen Biomedical Technology Co., Ltd. C. Zhang: Other, Personal, Full or part-time Employment: Shanghai Topgen Biomedical Technology Co., Ltd. All other authors have declared no conflicts of interest.