Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis

Thorsen, K., Sorensen, K. D., Brems-Eskildsen, A. S., Modin, C., Gaustadnes, M., Hein, A. M. K., Kruhoffer, M., Laurberg, S., Borre, M., Wang, K., Brunak, S., Krainer, A. R., Torring, N., Dyrskjot, L., Andersen, C. L., Orntoft, T. F. (July 2008) Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis. Molecular & Cellular Proteomics, 7 (7). pp. 1214-1224. ISSN 1535-9476

URL: http://www.ncbi.nlm.nih.gov/pubmed/18353764
DOI: 10.1074/mcp.M700590-MCP200

Abstract

Alternative splicing enhances proteome diversity and modulates cancer-associated proteins. To identify tissue- and tumor-specific alternative splicing, we used the GeneChip Human Exon 1.0 ST Array to measure whole-genome exon expression in 102 normal and cancer tissue samples of different stages from colon, urinary bladder, and prostate. We identified 2069 candidate alternative splicing events between normal tissue samples from colon, bladder, and prostate and selected 15 splicing events for RT-PCR validation, 10 of which were successfully validated by RT-PCR and sequencing. Furthermore 23, 19, and 18 candidate tumor-specific splicing alterations in colon, bladder, and prostate, respectively, were selected for RT-PCR validation on an independent set of 81 normal and tumor tissue samples. In total, seven genes with tumor-specific splice variants were identified (ACTN1, CALD1, COL6A3, LRRFIP2, PIK4CB, TPM1, and VCL). The validated tumor-specific splicing alterations were highly consistent, enabling clear separation of normal and cancer samples and in some cases even of different tumor stages. A subset of the tumor-specific splicing alterations (ACTN1, CALD1, and VCL) was found in all three organs and may represent general cancer-related splicing events. In silico protein predictions suggest that the identified cancers-pecific splice variants encode proteins with potentially altered functions, indicating that they may be involved in pathogenesis and hence represent novel therapeutic targets. In conclusion, we identified and validated alternative splicing between normal tissue samples from colon, bladder, and prostate in addition to cancer-specific splicing events in colon, bladder, and prostate cancer that may have diagnostic and prognostic implications.

Item Type: Paper
Uncontrolled Keywords: MESSENGER-RNA COLORECTAL-CANCER GENE-EXPRESSION CELL MOTILITY HUMAN GENOME PREDICTION ELEMENTS TRANSCRIPTOME CONSERVATION MICROARRAYS
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
diseases & disorders > cancer > cancer types > bladder cancer
diseases & disorders > cancer > cancer types > colon cancer
diseases & disorders > cancer > cancer types > colon cancer

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > exons > exon splicing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > introns > intron splicing
diseases & disorders > cancer > cancer types > prostate cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: July 2008
Date Deposited: 28 Feb 2013 16:52
Last Modified: 28 Feb 2013 16:52
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27489

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