Dataset Information

Exon-level expression profiling of normal colonic mucosa samples.

ABSTRACT: These samples have been analyzed for global alternative splicing variation on exon-level expression data using the FIRMA algorithm. We have identified and described transcriptome instability as a genome-wide, pre-mRNA splicing related characteristic of solid cancers. This Series consists of 19 normal colonic mucosa samples from colorectal cancer patients, and is an amendment to a larger series of colorectal cancer and adjacent normal colonic mucosa samples analyzed for gene expression at the exon-level (GSE24550).

OTHER RELATED OMICS DATASETS IN: PRJNA182912PRJNA183937

ORGANISM(S): Homo Sapiens

SUBMITTER: Ragnhild A Lothe Trude H Ågesen Arild Nesbakken Rolf I Skotheim Anita Sveen

PROVIDER: E-GEOD-42690 | ArrayExpress | 2014-08-13

SECONDARY ACCESSION(S): GSE42690PRJNA182912

REPOSITORIES: GEO, ArrayExpress

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Publications

Transcriptome instability as a molecular pan-cancer characteristic of carcinomas.

Sveen Anita A Johannessen Bjarne B Teixeira Manuel R MR Lothe Ragnhild A RA Skotheim Rolf I RI

BMC genomics 20140810

<h4>Background</h4>We have previously proposed transcriptome instability as a genome-wide, pre-mRNA splicing-related characteristic of colorectal cancer. Here, we explore the hypothesis of transcriptome instability being a general characteristic of cancer.<h4>Results</h4>Exon-level microarray expression data from ten cancer datasets were analyzed, including breast cancer, cervical cancer, colorectal cancer, gastric cancer, lung cancer, neuroblastoma, and prostate cancer (555 samples), as well as ...[more]

PMID: 25109687

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Project description:BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease that, on the molecular level, can be characterized by inherent genomic instabilities; chromosome instability and microsatellite instability. In the present study we analyze genome-wide disruption of pre-mRNA splicing, and propose transcriptome instability as a characteristic that is analogous to genomic instability on the transcriptome level. METHODS: Exon microarray profiles from two independent series including a total of 160 CRCs were investigated for their relative amounts of exon usage differences. Each exon in each sample was assigned an alternative splicing score calculated by the FIRMA algorithm. Amounts of deviating exon usage per sample were derived from exons with extreme splicing scores. RESULTS: There was great heterogeneity within both series in terms of sample-wise amounts of deviating exon usage. This was strongly associated with the expression levels of approximately half of 280 splicing factors (54% and 48% of splicing factors were significantly correlated to deviating exon usage amounts in the two series). Samples with high or low amounts of deviating exon usage, associated with overall transcriptome instability, were almost completely separated into their respective groups by hierarchical clustering analysis of splicing factor expression levels in both sample series. Samples showing a preferential tendency towards deviating exon skipping or inclusion were associated with skewed transcriptome instability. There were significant associations between transcriptome instability and reduced patient survival in both sample series. In the test series, patients with skewed transcriptome instability showed the strongest prognostic association (P = 0.001), while a combination of the two characteristics showed the strongest association with poor survival in the validation series (P = 0.03). CONCLUSIONS: We have described transcriptome instability as a characteristic of CRC. This transcriptome instability has associations with splicing factor expression levels and poor patient survival.

			Action	DRS
	E-GEOD-42690.idf.txt	Idf
	E-GEOD-42690.processed.1.zip	Processed
	E-GEOD-42690.raw.1.zip	Raw
	E-GEOD-42690.raw.2.zip	Raw
	E-GEOD-42690.raw.3.zip	Raw