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Germline genomic patterns are associated with cancer risk, oncogenic pathways, and clinical outcomes.

Authors
  • Xu, Xue1, 2, 3, 4
  • Zhou, Yuan5
  • Feng, Xiaowen2, 3, 4, 5
  • Li, Xiong2, 3, 4, 6
  • Asad, Mohammad2, 3, 4
  • Li, Derek2, 3, 4
  • Liao, Bo7
  • Li, Jianqiang8
  • Cui, Qinghua9
  • Wang, Edwin10, 3, 4
  • 1 College of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China. , (China)
  • 2 Department of Biochemistry and Molecular Biology, Medical Genetics, and Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. , (Canada)
  • 3 Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. , (Canada)
  • 4 Arnie Charbonneau Cancer Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. , (Canada)
  • 5 Department of Biomedical Informatics, School of Basic Medical Science, Peking University Health Science Center, Beijing, China. , (China)
  • 6 School of Software, East China Jiaotong University, Nanchang, China. , (China)
  • 7 School of Mathematics and Statistics, Hainan Normal University, Haikou, China. [email protected] [email protected] [email protected] [email protected] , (China)
  • 8 College of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China. [email protected] [email protected] [email protected] [email protected] , (China)
  • 9 Department of Biomedical Informatics, School of Basic Medical Science, Peking University Health Science Center, Beijing, China. [email protected] [email protected] [email protected] [email protected] , (China)
  • 10 Department of Biochemistry and Molecular Biology, Medical Genetics, and Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. [email protected] [email protected] [email protected] [email protected] , (Canada)
Type
Published Article
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Nov 01, 2020
Volume
6
Issue
48
Identifiers
DOI: 10.1126/sciadv.aba4905
PMID: 33246949
Source
Medline
Language
English
License
Unknown

Abstract

There is an ongoing debate on the importance of genetic factors in cancer development, where gene-centered cancer predisposition seems to show that only 5 to 10% of the cancer cases are inheritable. By conducting a systematic analysis of germline genomes of 9712 cancer patients representing 22 common cancer types along with 16,670 noncancer individuals, we identified seven cancer-associated germline genomic patterns (CGGPs), which summarized trinucleotide mutational spectra of germline genomes. A few CGGPs were consistently enriched in the germline genomes of patients whose tumors had smoking signatures or correlated with oncogenesis- and genome instability-related mutations. Furthermore, subgroups defined by the CGGPs were significantly associated with distinct oncogenic pathways, tumor histological subtypes, and prognosis in 13 common cancer types, suggesting that germline genomic patterns enable to inform treatment and clinical outcomes. These results provided evidence that cancer risk and clinical outcomes could be encoded in germline genomes. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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