Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells.
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Date
2017-08-29Author
Roumeliotis, TI
Williams, SP
Gonçalves, E
Alsinet, C
Del Castillo Velasco-Herrera, M
Aben, N
Ghavidel, FZ
Michaut, M
Schubert, M
Price, S
Wright, JC
Yu, L
Yang, M
Dienstmann, R
Guinney, J
Beltrao, P
Brazma, A
Pardo, M
Stegle, O
Adams, DJ
Wessels, L
Saez-Rodriguez, J
McDermott, U
Choudhary, JS
Type
Journal Article
Metadata
Show full item recordAbstract
Assessing the impact of genomic alterations on protein networks is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labeling to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the functional consequences of somatic genomic variants. The robust quantification of over 9,000 proteins and 11,000 phosphopeptides on average enabled the de novo construction of a functional protein correlation network, which ultimately exposed the collateral effects of mutations on protein complexes. CRISPR-cas9 deletion of key chromatin modifiers confirmed that the consequences of genomic alterations can propagate through protein interactions in a transcript-independent manner. Lastly, we leveraged the quantified proteome to perform unsupervised classification of the cell lines and to build predictive models of drug response in colorectal cancer. Overall, we provide a deep integrative view of the functional network and the molecular structure underlying the heterogeneity of colorectal cancer cells.
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Subject
Cell Line, Tumor
Humans
Colorectal Neoplasms
Neoplasm Proteins
Phosphoproteins
Protein Subunits
Proteome
RNA, Messenger
Antineoplastic Agents
Proteomics
Transcription, Genetic
Gene Expression Regulation, Neoplastic
Mutation
Quantitative Trait Loci
Genome, Human
Models, Biological
Research team
Functional Proteomics Group
Language
eng
Date accepted
2017-07-24
License start date
2017-08
Citation
Cell reports, 2017, 20 (9), pp. 2201 - 2214
Publisher
CELL PRESS