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Chromosomal rearrangements are commonly post-transcriptionally attenuated in cancer

View ORCID ProfileEmanuel Gonçalves, Athanassios Fragoulis, Luz Garcia-Alonso, Thorsten Cramer, View ORCID ProfileJulio Saez-Rodriguez, View ORCID ProfilePedro Beltrao
doi: https://doi.org/10.1101/093369
Emanuel Gonçalves
1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK
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  • ORCID record for Emanuel Gonçalves
Athanassios Fragoulis
3Molecular Tumor Biology, Department of General, Visceral and Transplantation Surgery, RWTH University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany
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Luz Garcia-Alonso
1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK
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Thorsten Cramer
3Molecular Tumor Biology, Department of General, Visceral and Transplantation Surgery, RWTH University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany
4NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
5ESCAM – European Surgery Center Aachen Maastricht, Germany and The Netherlands
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Julio Saez-Rodriguez
1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK
2RWTH Aachen University, Faculty of Medicine, Joint Research Centre for Computational Biomedicine, Aachen 52057, Germany
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  • For correspondence: saezrodriguez@gmail.com pedrobeltrao@ebi.ac.uk
Pedro Beltrao
1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK
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  • ORCID record for Pedro Beltrao
  • For correspondence: saezrodriguez@gmail.com pedrobeltrao@ebi.ac.uk
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Abstract

Chromosomal rearrangements, despite being detrimental, are ubiquitous in cancer and often act as driver events. The effect of copy number variations (CNVs) on the cellular proteome of tumours is poorly understood. Therefore, we have analysed recently generated proteogenomic data-sets on 282 tumour samples to investigate the impact of CNVs in the proteome of these cells. We found that CNVs are post-transcriptionally attenuated in 23-33% of proteins with an enrichment for protein complexes. Complex subunits are highly co-regulated and some act as rate-limiting steps of complex assembly, indirectly controlling the abundance of other complex members. We identified 48 such regulatory interactions and experimentally validated AP3B1 and GTF2E2 as controlling subunits. Lastly, we found that a gene-signature of protein attenuation is associated with increased resistance to chaperone and proteasome inhibitors. This study highlights the importance of post-transcriptional mechanisms in cancer which allow cells to cope with their altered genomes.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 01, 2017.
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Chromosomal rearrangements are commonly post-transcriptionally attenuated in cancer
Emanuel Gonçalves, Athanassios Fragoulis, Luz Garcia-Alonso, Thorsten Cramer, Julio Saez-Rodriguez, Pedro Beltrao
bioRxiv 093369; doi: https://doi.org/10.1101/093369
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Chromosomal rearrangements are commonly post-transcriptionally attenuated in cancer
Emanuel Gonçalves, Athanassios Fragoulis, Luz Garcia-Alonso, Thorsten Cramer, Julio Saez-Rodriguez, Pedro Beltrao
bioRxiv 093369; doi: https://doi.org/10.1101/093369

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