title: Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis.
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.
authors: Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, DK-8200 Aarhus N, Denmark.
authors: Kasper
authors: K
authors: Thorsen
authors: Karina D
authors: KD
authors: Sørensen
authors: Anne Sofie
authors: AS
authors: Brems-Eskildsen
authors: Charlotte
authors: C
authors: Modin
authors: Mette
authors: M
authors: Gaustadnes
authors: Anne-Mette K
authors: AM
authors: Hein
authors: Mogens
authors: M
authors: Kruhøffer
authors: Søren
authors: S
authors: Laurberg
authors: Michael
authors: M
authors: Borre
authors: Kai
authors: K
authors: Wang
authors: Søren
authors: S
authors: Brunak
authors: Adrian R
authors: AR
authors: Krainer
authors: Niels
authors: N
authors: Tørring
authors: Lars
authors: L
authors: Dyrskjøt
authors: Claus L
authors: CL
authors: Andersen
authors: Torben F
authors: TF
authors: Orntoft
mesh_terms: D000185:Actinin / Q000235:genetics / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017398:Alternative Splicing / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005091:Exons; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016596:Vinculin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C526905:ACTN1 protein, human; D002148:Calmodulin-Binding Proteins; C488955:VCL protein, human; D000185:Actinin; D016596:Vinculin