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

  • Panwen Tian
  • Xiangyang Cheng
  • Zhengyi Zhao
  • Yuzi Zhang
  • Celimuge Bao
  • Yanyan Wang
  • Shangli Cai
  • Guowei MaEmail author
  • Ying HuangEmail author
Short Communication


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.


Germline mutation Next-generation sequencing Lung cancer DNA damage repair pathway 



Drs. Zhengyi Zhao, Yuzi Zhang, Celimuge Bao, Yanyan Wang, and Shangli Cai are employees of 3D Medicines Inc. The remaining authors declare no conflict of interests.

Author Contributions

Conception and design: Panwen Tian, Xiangyang Cheng, Guowei Ma, and Ying Huang.

Analysis and interpretation of data: Zhengyi Zhao, Yuzi Zhang, Celimuge Bao, Yanyan Wang, and Shangli Cai.

Drafting the article: All authors.

Revising the article critically for important intellectual content: Guowei Ma, Ying Huang.

Ying Huang accepts full responsibility for the work and/or the conduct of the study, had access to the data, and oversaw the decision to publish.

Compliance with ethical standards


The author(s) received no specific funding for this work.


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Copyright information

© Arányi Lajos Foundation 2019

Authors and Affiliations

  1. 1.Department of Respiratory and Critical Care Medicine, West China HospitalSichuan UniversityChengduChina
  2. 2.The first affiliated hospital of Guangzhou medical universityGuangzhouChina
  3. 3.The Medical Department3D Medicines Inc.ShanghaiChina
  4. 4.The Information System Department3D Medicines Inc.ShanghaiChina
  5. 5.Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouChina
  6. 6.Department of RespiratoryFirst Affiliated Hospital of Army Military Medical UniversityChongqingChina

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