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

• Published in: Oncogene Vol. 29; no. 13; pp. 1997 - 2004
• Main Authors: Hofstetter, G, Berger, A, Fiegl, H, Slade, N, Zorić, A, Holzer, B, Schuster, E, Mobus, V J, Reimer, D, Daxenbichler, G, Marth, C, Zeimet, A G, Concin, N, Zeillinger, R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2010; Nature Publishing Group
• Subjects: 631/337/1645/1946; 631/67/1059/99; 692/53/2422; 692/699/67/1517/1709; Alternative splicing; Apoptosis; Cell Biology; Chemotherapy; Confidence intervals; Human Genetics; Internal Medicine; Isoforms; Medicine; Medicine & Public Health; Oncology; Ovarian cancer; p53 Protein; short-communication; Tumor cell lines; Tumor suppressor genes; Tumors; splice variants; ovarian cancer; p73; p53
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2009.482

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.