TY - JOUR
T1 - Cross-species identification of cancer resistance-associated genes that may mediate human cancer risk
AU - Ulhas Nair, Nishanth
AU - Cheng, Kuoyuan
AU - Naddaf, Lamis
AU - Sharon, Elad
AU - Pal, Lipika R.
AU - Rajagopal, Padma S.
AU - Unterman, Irene
AU - Aldape, Kenneth
AU - Hannenhalli, Sridhar
AU - Day, Chi Ping
AU - Tabach, Yuval
AU - Ruppin, Eytan
N1 - Publisher Copyright:
© 2022 American Association for the Advancement of Science. All rights reserved.
PY - 2022/8/5
Y1 - 2022/8/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85135459600&partnerID=8YFLogxK
U2 - 10.1126/sciadv.abj7176
DO - 10.1126/sciadv.abj7176
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C2 - 35921407
AN - SCOPUS:85135459600
SN - 2375-2548
VL - 8
JO - Science advances
JF - Science advances
IS - 31
M1 - eabj7176
ER -
