A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer
Abstract While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on “bystander” genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56301-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571554233319424 |
|---|---|
| author | Veronica Rendo Michael Schubert Nicholas Khuu Maria F. Suarez Peredo Rodriguez Declan Whyte Xiao Ling Anouk van den Brink Kaimeng Huang Michelle Swift Yizhou He Johanna Zerbib Ross Smith Jonne Raaijmakers Pratiti Bandopadhayay Lillian M. Guenther Justin H. Hwang Amanda Iniguez Susan Moody Ji-Heui Seo Elizabeth H. Stover Levi Garraway William C. Hahn Kimberly Stegmaier René H. Medema Dipanjan Chowdhury Maria Colomé-Tatché Uri Ben-David Rameen Beroukhim Floris Foijer |
| author_facet | Veronica Rendo Michael Schubert Nicholas Khuu Maria F. Suarez Peredo Rodriguez Declan Whyte Xiao Ling Anouk van den Brink Kaimeng Huang Michelle Swift Yizhou He Johanna Zerbib Ross Smith Jonne Raaijmakers Pratiti Bandopadhayay Lillian M. Guenther Justin H. Hwang Amanda Iniguez Susan Moody Ji-Heui Seo Elizabeth H. Stover Levi Garraway William C. Hahn Kimberly Stegmaier René H. Medema Dipanjan Chowdhury Maria Colomé-Tatché Uri Ben-David Rameen Beroukhim Floris Foijer |
| author_sort | Veronica Rendo |
| collection | DOAJ |
| description | Abstract While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on “bystander” genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed. Combining these approaches, we propose a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes located in commonly amplified regions, yet expressed at lower levels than expected by their copy number, and toxic when overexpressed. We validate RBM14 as an ARGOS gene in lung and breast cancer cells, and suggest a toxicity mechanism involving altered DNA damage response and STING signaling. We additionally observe increased patient survival in a radiation-treated cancer cohort with RBM14 amplification. |
| format | Article |
| id | doaj-art-e906141181664152b578d1feb5aade5c |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e906141181664152b578d1feb5aade5c2025-02-02T12:32:30ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-025-56301-2A compendium of Amplification-Related Gain Of Sensitivity genes in human cancerVeronica Rendo0Michael Schubert1Nicholas Khuu2Maria F. Suarez Peredo Rodriguez3Declan Whyte4Xiao Ling5Anouk van den Brink6Kaimeng Huang7Michelle Swift8Yizhou He9Johanna Zerbib10Ross Smith11Jonne Raaijmakers12Pratiti Bandopadhayay13Lillian M. Guenther14Justin H. Hwang15Amanda Iniguez16Susan Moody17Ji-Heui Seo18Elizabeth H. Stover19Levi Garraway20William C. Hahn21Kimberly Stegmaier22René H. Medema23Dipanjan Chowdhury24Maria Colomé-Tatché25Uri Ben-David26Rameen Beroukhim27Floris Foijer28Department of Medical Oncology and Center for Neuro-Oncology, Dana-Farber Cancer InstituteOncode Institute, Division of Cell Biology, The Netherlands Cancer InstituteDepartment of Medical Oncology and Center for Neuro-Oncology, Dana-Farber Cancer InstituteEuropean Research Institute for the Biology of Ageing, University Medical Center GroningenEuropean Research Institute for the Biology of Ageing, University Medical Center GroningenEuropean Research Institute for the Biology of Ageing, University Medical Center GroningenEuropean Research Institute for the Biology of Ageing, University Medical Center GroningenBroad Institute of Harvard and MITDepartment of Radiation Oncology, Dana-Farber Cancer InstituteBroad Institute of Harvard and MITDepartment of Human Molecular Genetics & Biochemistry, Faculty of Medicine, Tel Aviv UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityOncode Institute, Division of Cell Biology, The Netherlands Cancer InstituteHarvard Medical SchoolSt. Jude Children’s Research Hospital, Department of OncologyDivision of Hematology, Oncology, and Transplantation, University of MinnesotaDepartment of Cancer Biology, Perelman School of Medicine at the University of PennsylvaniaDepartment of Medical Oncology and Center for Neuro-Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology and Center for Neuro-Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology and Center for Neuro-Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology and Center for Neuro-Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology and Center for Neuro-Oncology, Dana-Farber Cancer InstituteHarvard Medical SchoolOncode Institute, Division of Cell Biology, The Netherlands Cancer InstituteBroad Institute of Harvard and MITInstitute of Computational Biology, Helmholtz MunichDepartment of Human Molecular Genetics & Biochemistry, Faculty of Medicine, Tel Aviv UniversityDepartment of Medical Oncology and Center for Neuro-Oncology, Dana-Farber Cancer InstituteEuropean Research Institute for the Biology of Ageing, University Medical Center GroningenAbstract While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on “bystander” genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed. Combining these approaches, we propose a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes located in commonly amplified regions, yet expressed at lower levels than expected by their copy number, and toxic when overexpressed. We validate RBM14 as an ARGOS gene in lung and breast cancer cells, and suggest a toxicity mechanism involving altered DNA damage response and STING signaling. We additionally observe increased patient survival in a radiation-treated cancer cohort with RBM14 amplification.https://doi.org/10.1038/s41467-025-56301-2 |
| spellingShingle | Veronica Rendo Michael Schubert Nicholas Khuu Maria F. Suarez Peredo Rodriguez Declan Whyte Xiao Ling Anouk van den Brink Kaimeng Huang Michelle Swift Yizhou He Johanna Zerbib Ross Smith Jonne Raaijmakers Pratiti Bandopadhayay Lillian M. Guenther Justin H. Hwang Amanda Iniguez Susan Moody Ji-Heui Seo Elizabeth H. Stover Levi Garraway William C. Hahn Kimberly Stegmaier René H. Medema Dipanjan Chowdhury Maria Colomé-Tatché Uri Ben-David Rameen Beroukhim Floris Foijer A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer Nature Communications |
| title | A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer |
| title_full | A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer |
| title_fullStr | A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer |
| title_full_unstemmed | A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer |
| title_short | A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer |
| title_sort | compendium of amplification related gain of sensitivity genes in human cancer |
| url | https://doi.org/10.1038/s41467-025-56301-2 |
| work_keys_str_mv | AT veronicarendo acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT michaelschubert acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT nicholaskhuu acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT mariafsuarezperedorodriguez acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT declanwhyte acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT xiaoling acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT anoukvandenbrink acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT kaimenghuang acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT michelleswift acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT yizhouhe acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT johannazerbib acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT rosssmith acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT jonneraaijmakers acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT pratitibandopadhayay acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT lillianmguenther acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT justinhhwang acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT amandainiguez acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT susanmoody acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT jiheuiseo acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT elizabethhstover acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT levigarraway acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT williamchahn acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT kimberlystegmaier acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT renehmedema acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT dipanjanchowdhury acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT mariacolometatche acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT uribendavid acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT rameenberoukhim acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT florisfoijer acompendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT veronicarendo compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT michaelschubert compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT nicholaskhuu compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT mariafsuarezperedorodriguez compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT declanwhyte compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT xiaoling compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT anoukvandenbrink compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT kaimenghuang compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT michelleswift compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT yizhouhe compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT johannazerbib compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT rosssmith compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT jonneraaijmakers compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT pratitibandopadhayay compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT lillianmguenther compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT justinhhwang compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT amandainiguez compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT susanmoody compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT jiheuiseo compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT elizabethhstover compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT levigarraway compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT williamchahn compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT kimberlystegmaier compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT renehmedema compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT dipanjanchowdhury compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT mariacolometatche compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT uribendavid compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT rameenberoukhim compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer AT florisfoijer compendiumofamplificationrelatedgainofsensitivitygenesinhumancancer |