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Cross-species identification of cancer resistance-associated genes that may mediate human cancer risk.
Nair, Nishanth Ulhas; Cheng, Kuoyuan; Naddaf, Lamis; Sharon, Elad; Pal, Lipika R; Rajagopal, Padma S; Unterman, Irene; Aldape, Kenneth; Hannenhalli, Sridhar; Day, Chi-Ping; Tabach, Yuval; Ruppin, Eytan.
Affiliation
  • Nair NU; Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
  • Cheng K; Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
  • Naddaf L; Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, USA.
  • Sharon E; Department of Developmental Biology and Cancer Research, Institute of Medical Research-Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Pal LR; Department of Developmental Biology and Cancer Research, Institute of Medical Research-Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Rajagopal PS; Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
  • Unterman I; Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
  • Aldape K; Department of Developmental Biology and Cancer Research, Institute of Medical Research-Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
  • Hannenhalli S; Laboratory of Pathology, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
  • Day CP; Cancer Data Science Laboratory (CDSL), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
  • Tabach Y; Laboratory of Cancer Biology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
  • Ruppin E; Department of Developmental Biology and Cancer Research, Institute of Medical Research-Israel-Canada, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel.
Sci Adv ; 8(31): eabj7176, 2022 08 05.
Article in En | MEDLINE | ID: mdl-35921407
ABSTRACT
Cancer is a predominant disease across animals. We applied a comparative genomics approach to systematically characterize genes whose conservation levels correlate positively (PC) or negatively (NC) with cancer resistance estimates across 193 vertebrates. Pathway analysis reveals that NC genes are enriched for metabolic functions and PC genes in cell cycle regulation, DNA repair, and immune response, pointing to their corresponding roles in mediating cancer risk. We find that PC genes are less tolerant to loss-of-function (LoF) mutations, are enriched in cancer driver genes, and are associated with germline mutations that increase human cancer risk. Their relevance to cancer risk is further supported via the analysis of mouse functional genomics and cancer mortality of zoo mammals' data. In sum, our study describes a cross-species genomic analysis pointing to candidate genes that may mediate human cancer risk.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genomics / Neoplasms Type of study: Diagnostic_studies / Etiology_studies / Risk_factors_studies Limits: Animals / Humans Language: En Journal: Sci Adv Year: 2022 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genomics / Neoplasms Type of study: Diagnostic_studies / Etiology_studies / Risk_factors_studies Limits: Animals / Humans Language: En Journal: Sci Adv Year: 2022 Document type: Article Affiliation country: United States