Cross-species identification of cancer resistance-associated genes that may mediate human cancer risk

Nishanth Ulhas Nair; Kuoyuan Cheng; Lamis Naddaf; Elad Sharon; Lipika R. Pal; Padma S. Rajagopal; Irene Unterman; Kenneth Aldape; Sridhar Hannenhalli; Chi Ping Day; Yuval Tabach; Eytan Ruppin

doi:10.1126/sciadv.abj7176

Cross-species identification of cancer resistance-associated genes that may mediate human cancer risk

Nishanth Ulhas Nair^*, Kuoyuan Cheng^*, Lamis Naddaf, Elad Sharon, Lipika R. Pal, Padma S. Rajagopal, Irene Unterman, Kenneth Aldape, Sridhar Hannenhalli, Chi Ping Day, Yuval Tabach^*, Eytan Ruppin^*

^*Corresponding author for this work

Department of Developmental Biology and Cancer Research

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	American English
Article number	eabj7176
Journal	Science advances
Volume	8
Issue number	31
DOIs	https://doi.org/10.1126/sciadv.abj7176
State	Published - Aug 2022

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© 2022 American Association for the Advancement of Science. All rights reserved.

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title = "Cross-species identification of cancer resistance-associated genes that may mediate human cancer risk",

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.",

author = "{Ulhas Nair}, Nishanth and Kuoyuan Cheng and Lamis Naddaf and Elad Sharon and Pal, {Lipika R.} and Rajagopal, {Padma S.} and Irene Unterman and Kenneth Aldape and Sridhar Hannenhalli and Day, {Chi Ping} and Yuval Tabach and Eytan Ruppin",

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doi = "10.1126/sciadv.abj7176",

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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

PY - 2022/8

Y1 - 2022/8

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.

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Cross-species identification of cancer resistance-associated genes that may mediate human cancer risk

Abstract

Bibliographical note

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