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

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

doi:10.1038/s41467-025-56301-2

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

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. StoverLevi Garraway, William C. Hahn, Kimberly Stegmaier, René H. Medema, Dipanjan Chowdhury, Maria Colomé-Tatché, Uri Ben-David, Rameen Beroukhim, Floris Foijer

Human Molecular Genetics Biochemistry

Tel Aviv University

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

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.

Original language	English
Article number	1077
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-56301-2
State	Published - Dec 2025

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-025-56301-2

Cite this

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., ... Foijer, F. (2025). A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer. Nature Communications, 16(1), Article 1077. https://doi.org/10.1038/s41467-025-56301-2

@article{e7508d143c7345ac92009e342eb21fd7,

title = "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 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 {\textquoteleft}Amplification-Related Gain Of Sensitivity{\textquoteright} (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.",

author = "Veronica Rendo and Michael Schubert and Nicholas Khuu and {Suarez Peredo Rodriguez}, {Maria F.} and Declan Whyte and Xiao Ling and {van den Brink}, Anouk and Kaimeng Huang and Michelle Swift and Yizhou He and Johanna Zerbib and Ross Smith and Jonne Raaijmakers and Pratiti Bandopadhayay and Guenther, {Lillian M.} and Hwang, {Justin H.} and Amanda Iniguez and Susan Moody and Seo, {Ji Heui} and Stover, {Elizabeth H.} and Levi Garraway and Hahn, {William C.} and Kimberly Stegmaier and Medema, {Ren{\'e} H.} and Dipanjan Chowdhury and Maria Colom{\'e}-Tatch{\'e} and Uri Ben-David and Rameen Beroukhim and Floris Foijer",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s41467-025-56301-2",

language = "الإنجليزيّة",

volume = "16",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Rendo, V, Schubert, M, Khuu, N, Suarez Peredo Rodriguez, MF, Whyte, D, Ling, X, van den Brink, A, Huang, K, Swift, M, He, Y, Zerbib, J, Smith, R, Raaijmakers, J, Bandopadhayay, P, Guenther, LM, Hwang, JH, Iniguez, A, Moody, S, Seo, JH, Stover, EH, Garraway, L, Hahn, WC, Stegmaier, K, Medema, RH, Chowdhury, D, Colomé-Tatché, M, Ben-David, U, Beroukhim, R & Foijer, F 2025, 'A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer', Nature Communications, vol. 16, no. 1, 1077. https://doi.org/10.1038/s41467-025-56301-2

TY - JOUR

T1 - A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer

AU - Rendo, Veronica

AU - Schubert, Michael

AU - Khuu, Nicholas

AU - Suarez Peredo Rodriguez, Maria F.

AU - Whyte, Declan

AU - Ling, Xiao

AU - van den Brink, Anouk

AU - Huang, Kaimeng

AU - Swift, Michelle

AU - He, Yizhou

AU - Zerbib, Johanna

AU - Smith, Ross

AU - Raaijmakers, Jonne

AU - Bandopadhayay, Pratiti

AU - Guenther, Lillian M.

AU - Hwang, Justin H.

AU - Iniguez, Amanda

AU - Moody, Susan

AU - Seo, Ji Heui

AU - Stover, Elizabeth H.

AU - Garraway, Levi

AU - Hahn, William C.

AU - Stegmaier, Kimberly

AU - Medema, René H.

AU - Chowdhury, Dipanjan

AU - Colomé-Tatché, Maria

AU - Ben-David, Uri

AU - Beroukhim, Rameen

AU - Foijer, Floris

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85217190281&partnerID=8YFLogxK

U2 - 10.1038/s41467-025-56301-2

DO - 10.1038/s41467-025-56301-2

M3 - مقالة

C2 - 39870664

SN - 2041-1723

VL - 16

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1077

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this