Multi-omics of 34 colorectal cancer cell lines - a resource for biomedical studies

Molecular Cancer

Research

Peter W. Eide¹  Guro E. Lind¹  Jarle Bruun¹  Kaja C. G. Berg¹  Ina A. Eilertsen¹  Merete Bjørnslett¹  Mette Eknæs¹  Rolf I. Skotheim²  Anita Sveen²  Stine A. Danielsen²  Ragnhild A. Lothe²  Bjarne Johannessen²  Leonardo A. Meza-Zepeda³  Ola Myklebost⁴ 

[1] Department of Molecular Oncology, Institute for Cancer Research & K.G.Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, P.O.Box 4953 Nydalen, -0424, Oslo, NO, Norway;Center for Cancer Biomedicine, Institute for Clinical Medicine, University of Oslo, Oslo, Norway;Department of Molecular Oncology, Institute for Cancer Research & K.G.Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, P.O.Box 4953 Nydalen, -0424, Oslo, NO, Norway;Center for Cancer Biomedicine, Institute for Clinical Medicine, University of Oslo, Oslo, Norway;Norwegian Cancer Genomic Consortium, Oslo University Hospital, Oslo, Norway;Norwegian Cancer Genomic Consortium, Oslo University Hospital, Oslo, Norway;Department of Core Facilities and Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway;Norwegian Cancer Genomic Consortium, Oslo University Hospital, Oslo, Norway;Department of Core Facilities and Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway;Department of Clinical Science, University of Bergen, Bergen, Norway;

关键词: Colorectal cancer cell lines;    Consensus molecular subtypes;    Copy number aberrations;    Gene expression;    Genomics;    Methylation;    Microsatellite instability;    miRNA;    Mutations;    Protein expression;   

DOI  :  10.1186/s12943-017-0691-y

 received in 2017-04-05, accepted in 2017-06-28,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundColorectal cancer (CRC) cell lines are widely used pre-clinical model systems. Comprehensive insights into their molecular characteristics may improve model selection for biomedical studies.MethodsWe have performed DNA, RNA and protein profiling of 34 cell lines, including (i) targeted deep sequencing (n = 612 genes) to detect single nucleotide variants and insertions/deletions; (ii) high resolution DNA copy number profiling; (iii) gene expression profiling at exon resolution; (iv) small RNA expression profiling by deep sequencing; and (v) protein expression analysis (n = 297 proteins) by reverse phase protein microarrays.ResultsThe cell lines were stratified according to the key molecular subtypes of CRC and data were integrated at two or more levels by computational analyses. We confirm that the frequencies and patterns of DNA aberrations are associated with genomic instability phenotypes and that the cell lines recapitulate the genomic profiles of primary carcinomas. Intrinsic expression subgroups are distinct from genomic subtypes, but consistent at the gene-, microRNA- and protein-level and dominated by two distinct clusters; colon-like cell lines characterized by expression of gastro-intestinal differentiation markers and undifferentiated cell lines showing upregulation of epithelial-mesenchymal transition and TGFβ signatures. This sample split was concordant with the gene expression-based consensus molecular subtypes of primary tumors. Approximately ¼ of the genes had consistent regulation at the DNA copy number and gene expression level, while expression of gene-protein pairs in general was strongly correlated. Consistent high-level DNA copy number amplification and outlier gene- and protein- expression was found for several oncogenes in individual cell lines, including MYC and ERBB2.ConclusionsThis study expands the view of CRC cell lines as accurate molecular models of primary carcinomas, and we present integrated multi-level molecular data of 34 widely used cell lines in easily accessible formats, providing a resource for preclinical studies in CRC.

【 授权许可】

CC BY   
© The Author(s). 2017