Abstract 2204: Spectrum of pathogenic germline mutations in Chinese head and neck cancer patients through next-generation sequencing
Authors: Gao Jianming , Zheng Yating , Xie Wenzhuan , Huang Mengli 
Published: July 2021

Abstract
Background: Head and neck cancer is currently a leading cause of cancer-associated mortality worldwide. Despite the increasing evidences of variants that were associated with head and neck cancer risk, investigations of genetic factors and their roles in genetic susceptibility to head and neck cancer were limited. The purpose of this study is to assess the inherited genetic factors regarding germline mutations in Chinese head and neck cancer population.
Methods: Genomic profiling of DNA was performed through a next-generation sequencing (NGS) (panel on 381/733-gene) on tissue from Chinese patients with head and neck cancer between January 06, 2017 and June 02 2020. 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).
Results: Of 357 patients with head and neck cancer, 325 (91.04%) patients were identified to carry 457 pathogenic or likely pathogenic germline mutations in 88 cancer predisposition genes, with a frequency of 91.09% (91/101) in nasopharyngeal carcinoma, and 91.41% (234/256) in non-nasopharyngeal carcinoma of the head and neck. In head and neck cancer patients, the most frequently germline mutated genes were CYP2C19 (56.92%), followed by DPYD (37.85 %), CYP2D6 (31.69%), RAC1 (29.85%), VEGFA (29.85%), MGMT (28%), CD74 (24.31%), BCL2L11 (11.69%), and APC (6.46%). Of all the 88 germline mutated genes, 27.27% (n=24) lay in the DNA damage repair (DDR) pathways. The highest frequency of DDR germline mutations was BARD1 (6.15%), followed by BRCA2 (6.15%), PLAB2 (5.54%),
FANCD2(5.23%), ATM(4.92%), FANCA (4.62%), RAD50 (4.62%), BRCA1(3.69%), MSH2 (3.38%), and MLH1 (3.08%). Of the 89 nasopharyngeal carcinoma patients with germline mutations that could be evaluated for MSI and TMB, only 1 (1.12%) patient was identified as MSI-H, and 3 (3.37%) patients had TMB≥10Muts/Mb. PD-L1 status analysis was performed in 77 nasopharyngeal carcinoma patients with germline mutated genes, and the results showed that 63 (81.81%) patients were PD-L1 positive (CPS≥1). In non-nasopharyngeal carcinoma with germline mutated genes, MSI status analysis was performed in 228 patients, and the results showed that 2 (0.87%) patient was identified as MSI-H. In addition, 108 (108/198, 27.6%) patients were PD-L1 positive (CPS≥1). Of the 229 non-nasopharyngeal carcinoma that could be evaluated for TMB, 54 (23.58%) patients had TMB≥10Muts/Mb.
Conclusions: Taken together, we have presented the spectrum of pathogenic germline mutations in a Chinese head and neck cancer cohort. The findings of inherited genetic variations may provide clues for the oncology treatment strategy and cancer prevention.
Citation Format: Jianming Gao, Yating Zheng, Wenzhuan Xie, Mengli Huang. Spectrum of pathogenic germline mutations in Chinese head and neck cancer patients 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 2204.