Korte synopsis
When chromosome fragments encoding oncogenes are amplified, the (focal) amplifications often exceed the coding sequence of the oncogene alone thus co-amplifying contain passenger genes. We performed a genome wide search of genes that are close to frequently amplified oncogenes, but for which uncompensated co-amplification is toxic. In other words, genes that cancer cells need to silence when they these are co-amplified. These genes, that we call ARGOS genes, potentially provide therapeutic vulnerabilities as their reactivation would be toxic to cancer cells. We identified RBM14 as an ARGOS gene and find that RBM14 is a modulator if the DNA damage response and cGAS STING signaling. In addition to revealing a new role for RBM14, our work provides a resource to the field of commonly amplified toxic genes that potentially can be exploited as therapeutic targets in aneuploid cancers.
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#.
A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer. Nat Commun. 2025 Jan 27;16(1):1077.
