Dataset Information

Genomic determinants of protein abundance variation in colorectal cancer cell lines

ABSTRACT: Assessing the impact of genomic alterations on protein networks is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labelling 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Jyoti Choudhary

PROVIDER: MSV000081528 | MassIVE |

SECONDARY ACCESSION(S): PXD005235

REPOSITORIES: MassIVE

ACCESS DATA

Publications

Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells.

Roumeliotis Theodoros I TI Williams Steven P SP Gonçalves Emanuel E Alsinet Clara C Del Castillo Velasco-Herrera Martin M Aben Nanne N Ghavidel Fatemeh Zamanzad FZ Michaut Magali M Schubert Michael M Price Stacey S Wright James C JC Yu Lu L Yang Mi M Dienstmann Rodrigo R Guinney Justin J Beltrao Pedro P Brazma Alvis A Pardo Mercedes M Stegle Oliver O Adams David J DJ Wessels Lodewyk L Saez-Rodriguez Julio J McDermott Ultan U Choudhary Jyoti S JS

Cell reports 20170801 9

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 ultimat ...[more]

PMID: 28854368

Similar Datasets

Project description:Human colorectal cancer (CRC) cell lines are a used widely-used to model system for investigation investigate of tumour biology, experimental therapytherapeutic and biomarkers discovery. However, to what extent these established CRC cell lines represent and maintain the genetic diversity of primary cancers is uncertain. In this study, we analyzed 70 CRC cell lines were analysed for mutations using whole exome sequencing and DNA copy-number using by whole-exome sequencing and SNP microarray profilings, respectively. Presence of gGene expression was defined using RNA-Seq. Data from cellCell line datas were was compared to those that published from for primary CRCs published by in The the Cancer Genome Atlas Network. Notably, we found that The spectrum of exome mutations and DNA copy-number aberrations spectra in 70 CRC cell lines closely resembled those seen inat of primary colorectal tumours. Similarities included the presence of at least two hypermutation phenotypes, as defined by signatures of for defective DNA mismatch repair and DNA polymerase ? (POLE) proof-reading deficiency, and along with concordant mutation profiles in the broadly altered WNT, MAPK, PI3K, TGF? and p53 pathways. In additionFurther, we documented mutations were enriched in genes involved in chromatin remodelling (ARID1A, CHD6, SRCAP) and histone methylation or acetylation (ASH1L, EP300, EP400, MLL2, MLL3, PRDM2, TRRAP). Chromosomal instability was prevalent in non-hypermutated cases, with similar patterns of whole, partial and focal chromosomal aberrations and overlapping significant minimal regions ofchromosomal gains and losses. While paired cell lines derived from the same tumour were found to exhibited considerable mutation and DNA copy-number differences, in silico simulations suggest that these differenceslargely mainly reflected a pre-existing heterogeneity in the tumour cells heterogeneity. In conclusion, our results establish that human CRC lines are representative of the main subtypes of primary tumours at the genomic level, further validating underscoring their utility as tools for to investigating investigate CRC biology and drug responses. 69 colorectal cancer cell lines were analysed for DNA copy number profiles.

Dataset Information

Genomic determinants of protein abundance variation in colorectal cancer cell lines

Publications

Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure