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Alternative splicing of p53 and p73: the novel p53 splice variant p53δ is an independent prognostic marker in ovarian cancer

Oncogene volume 29, pages 1997–2004 (2010)Cite this article

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Abstract

Similar to p73, the tumor suppressor gene p53 is subject to alternative splicing. Besides p53ΔE6 and p53β, we identified p53ζ, p53δ and p53ɛ, arising from alternative splicing of exon 6 and intron 9, respectively. p53 splice variants were present in 18 of 34 ovarian cancer cell lines (52.9%) and 134 of 245 primary ovarian cancers (54.7%). p53δ expression was associated with impaired response to primary platinum-based chemotherapy (P=0.032). Also, p53δ expression constituted an independent prognostic marker for recurrence-free and overall survival (hazard ratio 1.854, 95% confidence interval 1.121–3.065, P=0.016; and hazard ratio 1.937, 95% confidence interval 1.177–3.186, P=0.009, respectively). p53β expression was associated with adverse clinicopathologic markers, that is, serous and poorly differentiated cancers (P=0.002 and P=0.008, respectively), and correlated with worse recurrence-free survival in patients exhibiting functionally active p53 (P=0.049). ΔN′p73 constituted the main N-terminally truncated p73 isoform and was preferentially found in ovarian cancer cell lines showing functionally active p53, supporting our hypothesis that N-terminally truncated p73 isoforms can alleviate the selection pressure for p53 mutations by the inhibition of p53 protein function.

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Acknowledgements

We thank Andrea Wolf for her technical assistance.

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Author notes

  1. G Hofstetter and A Berger: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Innsbruck Medical University, Innsbruck, Austria

    G Hofstetter, A Berger, H Fiegl, D Reimer, G Daxenbichler, C Marth, A G Zeimet & N Concin

  2. Department of Molecular Medicine, Laboratory of Molecular Oncology, Rudjer Boskovic Institute, Zagreb, Croatia

    N Slade & A Zorić

  3. Department of Obstetrics and Gynecology, Molecular Oncology Group, Medical University of Vienna, Vienna, Austria

    B Holzer, E Schuster & R Zeillinger

  4. Department of Obstetrics and Gynecology, Staedtische Kliniken, Frankfurt, Germany

    V J Mobus

  5. Ludwig Boltzmann Gesellschaft, Cluster Translational Oncology, Vienna, Austria

    R Zeillinger

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  1. G Hofstetter
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  2. A Berger
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  3. H Fiegl
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Corresponding author

Correspondence to R Zeillinger.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Hofstetter, G., Berger, A., Fiegl, H. et al. Alternative splicing of p53 and p73: the novel p53 splice variant p53δ is an independent prognostic marker in ovarian cancer. Oncogene 29, 1997–2004 (2010). https://doi.org/10.1038/onc.2009.482

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  • DOI: https://doi.org/10.1038/onc.2009.482

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