Spectrum of Pathogenic Germline Mutations in Chinese Lung Cancer Patients through Next-Generation Sequencing

[摘要] Lung cancer is currently a leading cause of cancer-associated mortality worldwide. Despite the increasing evidences of variants that were associated with lung cancer risk, investigations of genetic factors and their roles in genetic susceptibility to lung cancer were limited. Here we systematically investigated the spectrum of pathogenic germline mutations in Chinese population with lung cancer. Genomic profiling of DNA was performed through next-generation sequencing (NGS) on tissue biopsy from 1764 Chinese lung cancer patients with a 381 cancer gene panel between January 01, 2017 and May 07, 2019. Patients with germline mutations were identified, and their clinical information were collected. Of 1764 patients with lung cancer, 67 (3.8%) patients were identified to carry pathogenic or likely pathogenic germline mutations in 25 cancer predisposition genes, with a frequency of 3.6% in lung adenocarcinoma (49/1349), 4.3% in squamous cell lung cancer (14/322), 5.6% in small cell lung cancer (4/72), and none in lung adenosquamous carcinoma (0/21), respectively. The highest pathogenic germline mutational prevalence were found in BRCA2 (0.79%), CHEK2 (0.40%), BRCA1 (0.34%), and TP53 (0.34%). Two splice mutations were reported for the first time in this study. Notably, a majority (85.5%) of the detected germline mutations fell in DNA damage repair pathways.

[关键词] Germline mutation;Next-generation sequencing;Lung cancer;DNA damage repair pathway