Abstract 1492P
Background
DNA damage repair (DDR) pathway alteration is known as a predictive biomarker of platinum-based chemotherapy, immunotherapy, and radiotherapy sensitivity in several kinds of cancer. In addition, mutations in the DDR gene have also been reported in several cancer. However, the predictive value and mutations of DDR in patients with esophageal squamous cell carcinoma (ESCC) is still uncertain. The purpose of this study is to determine the frequency of DDR mutations, and the correlation between DDR and immunogenic biomarker in Chinese ESCC patients.
Methods
Tumor tissue samples from Chinese ESCC were analyzed using next generation sequencing (NGS) (panel on 381/733-gene). TMB was defined as total number of somatic non-synonymous mutations in coding region. MSI was evaluated by NGS of 500 known MSI loci. PD-L1 expression was evaluated using immunohistochemistry (Dako 22C3). Germline or somatic mutations of 80 DDR genes were classified as DDR gene mutations.
Results
Genetic mutation of 235 ESCC patients were analyzed using NGS, of which 24 (10.21%) harbored alterations in DDR genes. Mutations in BRCA2, BRIP1, ERCC1, MLH1, MSH6, PALB2, PRKDC, RAD51, SHPRH, ATR, BLM, BRCA1, CHEK2, FANCA, and ATM were mutually exclusive. The most frequently mutated DDR genes were ATM (2.54%), followed by FANCA (1.52%) and CHEK2 (1.52%). Then, the ESCC patients were subdivided into DDR mutations (MUT) and wild-type (WT), there was no significant difference in the mutation frequency of genes other than the DDR gene between DDR MUT and DDR WT. And there was no difference on PD-L1 expression (P=0.16) and TMB (p=0.28) between DDR MUT and DDR WT. Finally, the MSI status of all 235 ESCC patients was detected, and the results showed that all patients were MSS.
Conclusions
We determined the frequency of DDR gene mutations in a series of Chinese ESCC patients, and found that there was no significant difference in PD-L1 expression, TMB and MSI status between the DDR MUT and DDR WT. These findings provide a theoretical basis for the future clinical study of DDR genes in predicting the efficacy of platinum-based chemotherapy, immunotherapy, and radiotherapy in Chinese ESCC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital& Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College.
Funding
Has not received any funding.
Disclosure
Y. Zheng, W. Xie, M. Huang: Full/Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.