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; Michael Borre; Kai Wang; Søren Brunak; Adrian R Krainer; Niels Tørring; Lars Dyrskjøt; Claus L Andersen; Torben Falck Ørntoft

doi:10.1074/mcp.M700590-MCP200

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, Michael Borre, Kai Wang, Søren Brunak, Adrian R Krainer, Niels Tørring, Lars Dyrskjøt, Claus L Andersen, Torben Falck Ørntoft

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

186 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 and Cellular Proteomics
Volume	7
Issue	7
Pages (from-to)	1214-24
Number of pages	10
ISSN	1535-9476
DOIs	https://doi.org/10.1074/mcp.M700590-MCP200
Publication status	Published - 2008

Keywords

Actinin
Adenoma
Alternative Splicing
Calmodulin-Binding Proteins
Colonic Neoplasms
Exons
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Male
Models, Molecular
Neoplasm Staging
Oligonucleotide Array Sequence Analysis
Prostatic Neoplasms
Urinary Bladder Neoplasms
Vinculin

Access to Document

10.1074/mcp.M700590-MCP200

Cite this

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

@article{6b8a4040c6ac11dd9710000ea68e967b,

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.",

keywords = "Actinin, Adenoma, Alternative Splicing, Calmodulin-Binding Proteins, Colonic Neoplasms, Exons, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Models, Molecular, Neoplasm Staging, Oligonucleotide Array Sequence Analysis, Prostatic Neoplasms, Urinary Bladder Neoplasms, Vinculin",

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

year = "2008",

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

language = "English",

volume = "7",

pages = "1214--24",

journal = "Molecular and Cellular Proteomics",

issn = "1535-9476",

publisher = "American Society for Biochemistry and Molecular Biology Inc.",

number = "7",

}

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

Alternative splicing in colon, bladder, and prostate cancer identified by exon array analysis. / Thorsen, Kasper ; Sørensen, Karina D ; Brems-Eskildsen, Anne Sofie et al.
In: Molecular and Cellular Proteomics, Vol. 7, No. 7, 2008, p. 1214-24.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

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

AU - Thorsen, Kasper

AU - Sørensen, Karina D

AU - Brems-Eskildsen, Anne Sofie

AU - Modin, Charlotte

AU - Gaustadnes, Mette

AU - Hein, Anne-Mette K

AU - Kruhøffer, Mogens

AU - Laurberg, Søren

AU - Borre, Michael

AU - Wang, Kai

AU - Brunak, Søren

AU - Krainer, Adrian R

AU - Tørring, Niels

AU - Dyrskjøt, Lars

AU - Andersen, Claus L

AU - Ørntoft, Torben Falck

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.

KW - Actinin

KW - Adenoma

KW - Alternative Splicing

KW - Calmodulin-Binding Proteins

KW - Colonic Neoplasms

KW - Exons

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Male

KW - Models, Molecular

KW - Neoplasm Staging

KW - Oligonucleotide Array Sequence Analysis

KW - Prostatic Neoplasms

KW - Urinary Bladder Neoplasms

KW - Vinculin

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

Keywords

Access to Document

Fingerprint

Cite this