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Alternative splicing and biological heterogeneity in prostate cancer

Nature Reviews Urology volume 6, pages 454–460 (2009)Cite this article

Abstract

The biological diversity of prostate cancer confounds standardization of therapy. Advances in molecular profiling suggest that differences in the genetic composition of tumors significantly contribute to the complexity of the disease. Alternative pre-mRNA splicing is a key genetic process underlying biological diversity. During alternative splicing, coding and noncoding regions of a single gene are rearranged to generate several messenger RNA transcripts yielding distinct protein isoforms with differing biological functions. Misregulation of the splicing machinery and mutations in key regulatory elements affect splicing of cancer-relevant genes. In prostate cancer, aberrant and alternative splicing generates proteins that influence cell phenotypes and survival of patients. Splicing events may be exploited for clinical benefit, and technological advances are beginning to uncover novel biomarkers and therapeutic targets. Since splicing mediates information transfer from the genome to the proteome, it adds an important dimension to '-omics'-based molecular signatures used to individualize care of patients.

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Figure 1: Alternative splicing.
Figure 2: Alternative splicing events.
Figure 3: Aberrant and alternative splicing events in prostate cancer.
Figure 4: Technological advances in alternative splicing discovery.

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Acknowledgements

P. Rajan was supported during a recent PhD tenure by a Medical Research Council Clinical Research Training Fellowship and a Royal College of Surgeons of England Surgical Research Fellowship. D. J. Elliott and H. Y. Leung currently hold an Association for International Cancer Research project grant.

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Authors and Affiliations

  1. Beatson Institute for Cancer Research, Glasgow, UK

    Prabhakar Rajan & Hing Y. Leung

  2. Institute of Human Genetics, Newcastle University, Newcastle-upon-Tyne, UK

    David J. Elliott

  3. Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, UK

    Craig N. Robson

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  1. Prabhakar Rajan
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  2. David J. Elliott
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  3. Craig N. Robson
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  4. Hing Y. Leung
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Correspondence to Prabhakar Rajan.

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Rajan, P., Elliott, D., Robson, C. et al. Alternative splicing and biological heterogeneity in prostate cancer. Nat Rev Urol 6, 454–460 (2009). https://doi.org/10.1038/nrurol.2009.125

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