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

Kasper Thorsen, Karina D. Sørensen, Anne Sofie Brems-Eskildsen, Charlotte Modin, Mette Gaustadnes, Anne-Mette K. Hein, Mogens Kruhøffer, Søren Laurberg, Kai Wang, Søren Brunak, Adrian R. Krainer, Niels Tørring, Lars Dyrskjøt, Claus L. Andersen, Torben F. Ørntoft

    Research output: Contribution to journalJournal articleResearchpeer-review

    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 cancer-specific 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.
    Original languageEnglish
    JournalMolecular and Cellular Proteomics
    Volume7
    Issue number7
    Pages (from-to)1214-1224
    ISSN1535-9476
    DOIs
    Publication statusPublished - 2008

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