Widespread Post-transcriptional Attenuation of Genomic Copy-Number Variation in Cancer

• DOI: 10.1016/j.cels.2017.08.013
• Publication Date: 2017-10-13T10:19:26Z
• Authors: Emanuel Gonçalves; Athanassios Frago...; Luz Garcia-Alonso; Thorsten Cramer; Julio Saez-Rodriguez; Pedro Beltrao
• Keywords: Proteomics; 0301 basic medicine; DNA Copy Number Variations; Proteome; Article; Cell Line; 03 medical and health sciences; Cell Line, Tumor; Neoplasms; BREAST-CANCER; Humans; PROTEOGENOMIC CHARACTERIZATION; COMPREHENSIVE RESOURCE; RNA Processing, Post-Transcriptional; Genome; LANDSCAPE; GENE ONTOLOGY; PROTEIN COMPLEX; Genomics; DEGRADATION; HCT116 Cells; 3. Good health; HEK293 Cells; X-CHROMOSOME; RNA; TRANSLATION; Transcriptome

Copy-number variations (CNVs) are ubiquitous in cancer and often act as driver events, but the effects of CNVs on the proteome of tumors are poorly understood. Here, we analyze recently published genomics, transcriptomics, and proteomics datasets made available by CPTAC and TCGA consortia on 282 breast, ovarian, and colorectal tumor samples to investigate the impact of CNVs in the proteomes of these cells. We found that CNVs are buffered by post-transcriptional regulation in 23%–33% of proteins that are significantly enriched in protein complex members. Our analyses show that complex subunits are highly co-regulated, and some act as rate-limiting steps of complex assembly, as their depletion induces decreased abundance of other complex members. We identified 48 such rate-limiting interactions and experimentally confirmed our predictions on the interactions of AP3B1 with AP3M1 and GTF2E2 with GTF2E1. This study highlights the importance of post-transcriptional mechanisms in cancer that allow cells to cope with their altered genomes.<br/>ISSN:2405-4720<br/>Cell Systems, 5 (4)<br/>