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

Kasper Thorsen; Karina Sørensen; Anne Sofie Brems-Eskildsen; Charlotte Modin; Mette Gaustadnes; Anne-Mette Krabbe Hein; Søren Brunak; Mogens Kruhøffer; Søren Laurberg; Michael Skov Borre; Kai Wang; Adrian R Krainer; Niels Tørring; Lars Dyrskjøt; Claus Andersen; Torben F Orntoft

doi:10.1074/mcp.M700590-MCP200

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

Kasper Thorsen, Karina Sørensen, Anne Sofie Brems-Eskildsen, Charlotte Modin, Mette Gaustadnes, Anne-Mette Krabbe Hein, Søren Brunak, Mogens Kruhøffer, Søren Laurberg, Michael Skov Borre, Kai Wang, Adrian R Krainer, Niels Tørring, Lars Dyrskjøt, Claus Andersen, Torben F Orntoft

161 Citations (Scopus)

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 language	English
Journal	Molecular & Cellular Proteomics
Volume	7
Issue number	7
Pages (from-to)	1214-24
Number of pages	11
ISSN	1535-9484
DOIs	https://doi.org/10.1074/mcp.M700590-MCP200
Publication status	Published - 2008
Externally published	Yes

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Thorsen, K., Sørensen, K., Brems-Eskildsen, A. S., Modin, C., Gaustadnes, M., Hein, A-M. K., Brunak, S., Kruhøffer, M., Laurberg, S., Borre, M. S., Wang, K., Krainer, A. R., Tørring, N., Dyrskjøt, L., Andersen, C., & Orntoft, T. F. (2008). Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis. Molecular & Cellular Proteomics, 7(7), 1214-24. https://doi.org/10.1074/mcp.M700590-MCP200

Thorsen, K, Sørensen, K, Brems-Eskildsen, AS, Modin, C, Gaustadnes, M, Hein, A-MK, Brunak, S, Kruhøffer, M, Laurberg, S, Borre, MS, Wang, K, Krainer, AR, Tørring, N, Dyrskjøt, L, Andersen, C & Orntoft, TF 2008, 'Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis', Molecular & Cellular Proteomics, vol. 7, no. 7, pp. 1214-24. https://doi.org/10.1074/mcp.M700590-MCP200

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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.",

author = "Kasper Thorsen and Karina S{\o}rensen and Brems-Eskildsen, {Anne Sofie} and Charlotte Modin and Mette Gaustadnes and Hein, {Anne-Mette Krabbe} and S{\o}ren Brunak and Mogens Kruh{\o}ffer and S{\o}ren Laurberg and Borre, {Michael Skov} and Kai Wang and Krainer, {Adrian R} and Niels T{\o}rring and Lars Dyrskj{\o}t and Claus Andersen and Orntoft, {Torben F}",

year = "2008",

doi = "10.1074/mcp.M700590-MCP200",

language = "English",

volume = "7",

pages = "1214--24",

journal = "Molecular and Cellular Proteomics",

issn = "1535-9476",

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TY - JOUR

T1 - Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis

AU - Thorsen, Kasper

AU - Sørensen, Karina

AU - Brems-Eskildsen, Anne Sofie

AU - Modin, Charlotte

AU - Gaustadnes, Mette

AU - Hein, Anne-Mette Krabbe

AU - Brunak, Søren

AU - Kruhøffer, Mogens

AU - Laurberg, Søren

AU - Borre, Michael Skov

AU - Wang, Kai

AU - Krainer, Adrian R

AU - Tørring, Niels

AU - Dyrskjøt, Lars

AU - Andersen, Claus

AU - Orntoft, Torben F

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1074/mcp.M700590-MCP200

DO - 10.1074/mcp.M700590-MCP200

M3 - Journal article

C2 - 18353764

SN - 1535-9476

VL - 7

SP - 1214

EP - 1224

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

IS - 7

ER -

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

Abstract

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