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

• Published in: Oncogene Vol. 29; no. 13; p. 1997
• Main Authors: Hofstetter, G, Berger, A, Fiegl, H, Slade, N, Zoric, 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: New York Nature Publishing Group 01.04.2010
• Subjects: Cellular biology; Gene expression; Medical prognosis; Ovarian cancer; Proteins
• 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 p53DeltaE6 and p53beta, we identified p53zeta, p53delta and p53varepsilon, 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%). p53delta expression was associated with impaired response to primary platinum-based chemotherapy (P=0.032). Also, p53delta 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). p53beta 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). DeltaN'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. [PUBLICATION ABSTRACT]