2021
DOI: 10.1101/2021.12.05.471308
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Regulation of protein complex partners as a compensatory mechanism in aneuploid tumors

Abstract: Aneuploidy, a state of chromosome imbalance, is a hallmark of human tumors, but its role in cancer still remains to be fully elucidated. To understand the consequences of whole chromosome-level aneuploidies on the proteome, we integrated aneuploidy, transcriptomic and proteomic data from hundreds of TCGA/CPTAC tumor samples. We found a surprisingly large number of expression changes happened on other, non-aneuploid chromosomes. Moreover, we identified an association between those changes and co-complex members… Show more

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Cited by 2 publications
(8 citation statements)
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“…Intriguingly, the effect of aneuploidy on RNA metabolism is not limited to the gained chromosomes or to protein complex genes, as we did not observe increased RNA degradation of transcripts from such genes. These findings are consistent with recent reports that dosage compensation of protein complex genes mostly occurs at the protein regulation level 5,6 . How aneuploid cells evolve to alter their global RNA metabolism in response to changes in gene dosage remains to be fully understood.…”
Section: Discussionsupporting
confidence: 93%
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“…Intriguingly, the effect of aneuploidy on RNA metabolism is not limited to the gained chromosomes or to protein complex genes, as we did not observe increased RNA degradation of transcripts from such genes. These findings are consistent with recent reports that dosage compensation of protein complex genes mostly occurs at the protein regulation level 5,6 . How aneuploid cells evolve to alter their global RNA metabolism in response to changes in gene dosage remains to be fully understood.…”
Section: Discussionsupporting
confidence: 93%
“…These data argue that buffering mechanisms might be at play in aneuploid cells to limit the burden brought about by an imbalanced karyotype. Although this stoichiometric control has been extensively studied at the protein level in the context of aneuploidy — in both untransformed 710,12,17,19,5557 and cancer cells 4,5 – the role and the impact of RNA metabolism regulation in controlling gene expression is only beginning to emerge as another important layer of regulation 23,58,59 . Interestingly, dosage compensation at the mRNA level seems to be minimal in yeast 13,20 , but has been recently observed in human cells 4,6 .…”
Section: Discussionmentioning
confidence: 99%
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“…Quantitative mass spectrometry has enabled the identification of DC at the level of protein abundance (Stingele et al 2012;Dephoure et al 2014;Ishikawa et al 2017;Taggart et al 2020;Schukken and Sheltzer 2022;Senger et al 2022). At the protein level, work in yeast has suggested 10-20% of gene amplifications have significant DC (Dephoure et al 2014;Ishikawa et al 2017), although genetic differences are a known source of variance (Larrimore et al 2020;Hose et al 2020).…”
Section: Introductionmentioning
confidence: 99%