Identification of pathogenic germline variants in a large Chinese lung cancer cohort by clinical sequencing.

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  • Additional Information
    • Source:
      Publisher: John Wiley & Sons, Inc Country of Publication: United States NLM ID: 101308230 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-0261 (Electronic) Linking ISSN: 15747891 NLM ISO Abbreviation: Mol Oncol Subsets: MEDLINE
    • Publication Information:
      Publication: 2017- : Hoboken, New Jersey : John Wiley & Sons, Inc.
      Original Publication: Amsterdam : Elsevier
    • Subject Terms:
      Lung Neoplasms*/genetics ; Lung Neoplasms*/pathology ; Germ-Line Mutation* ; Genetic Predisposition to Disease* ; Asian People*/genetics; Humans ; Male ; Female ; Middle Aged ; Aged ; Cohort Studies ; Adult ; High-Throughput Nucleotide Sequencing ; Case-Control Studies ; China ; East Asian People
    • Abstract:
      Genetic factors play significant roles in the tumorigenicity of lung cancer; however, there is lack of systematic and large-scale characterization of pathogenic germline variants for lung cancer. In this study, germline variants in 146 preselected cancer-susceptibility genes were detected in 17 904 Chinese lung cancer patients by clinical next-generation sequencing. Among 17 904 patients, 1738 patients (9.7%) carried 1840 pathogenic/likely pathogenic (P/LP) variants from 87 cancer-susceptibility genes. SBDS (SBDS ribosome maturation factor) (1.37%), TSHR (thyroid stimulating hormone receptor) (1.20%), BLM (BLM RecQ like helicase) (0.62%), BRCA2 (BRCA2 DNA repair associated) (0.62%), and ATM (ATM serine/threonine kinase) (0.45%) were the top five genes with the highest overall prevalence. The top mutated pathways were all involved in DNA damage repair (DDR). Case-control analysis showed SBDS c.184A>T(p.K62*), TSHR c.1574T>C(p.F525S), BRIP1 (BRCA1 interacting helicase 1) c.1018C>T(p.L340F), and MUTYH (mutY DNA glycosylase) c.55C>T(p.R19*) were significantly associated with increased lung cancer risk (q value < 0.05). P/LP variants in certain genes were associated with early onset of lung cancer. Our study indicates that Chinese lung cancer patients have a higher prevalence of P/LP variants than previously reported. P/LP variants are distributed in multiple pathways and dominated by DNA damage repair-associated pathways. The association between identified P/LP variants and lung cancer risk requires further studies for verification.
      (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
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    • Grant Information:
      HXKT20231002 The Beijing Medical Public Welfare Foundation; ZKX21015 Nanjing City Key Medical Science and Technology Project Plan
    • Contributed Indexing:
      Keywords: DNA damage repair; germline variant; hereditary cancer syndrome; lung cancer
    • Publication Date:
      Date Created: 20231027 Date Completed: 20240508 Latest Revision: 20240709
    • Publication Date:
      20240709
    • Accession Number:
      PMC11076998
    • Accession Number:
      10.1002/1878-0261.13548
    • Accession Number:
      37885353