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Rendo, V.* ; Schubert, M. ; Khuu, N.* ; Suarez Peredo Rodriguez, M.F.* ; Whyte, D.* ; Ling, X.* ; van den Brink, A.* ; Huang, K.* ; Swift, M.* ; He, Y.* ; Zerbib, J.* ; Smith, R.* ; Raaijmakers, J.* ; Bandopadhayay, P.* ; Guenther, L.M.* ; Hwang, J.H.* ; Iniguez, A.* ; Moody, S.* ; Seo, J.H.* ; Stover, E.H.* ; Garraway, L.* ; Hahn, W.C.* ; Stegmaier, K.* ; Medema, R.H.* ; Chowdhury, D.* ; Colomé-Tatché, M. ; Ben-David, U.* ; Beroukhim, R.* ; Foijer, F.*

A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer.

Nat. Commun. 16:1077 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Therapeutic Vulnerabilities; Dosage Sensitivity; Protein; Resistance; Dependency; Generation; Senescence; Deletion; Kinase; Enzyme
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 16, Issue: 1, Pages: , Article Number: 1077 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-554200-001
Grants Marie Sklstrok
Break Through Cancer
Gray Matters Brain Cancer Foundation
NIH
ERC Starting Grant
Swedish Research Council
Brain Tumor Charity
Dutch Cancer Society
odowska-Curie postdoctoral fellowship
odowska-Curie postdoctoral fellowship (101068734)
Brown Fund for Innovative Cancer Informatics
DOI 10.1038/s41467-025-56301-2
WOS ID 001408553700011
PubMed ID 39870664
Erfassungsdatum 2025-03-26
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