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

Similar to p73, the tumor suppressor gene p53 is subject to alternative splicing. Besides p53 Delta E6 and p53 beta, we identified p53 zeta, p53 delta and p53 epsilon, 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%). p53 delta expression was associated with impaired response to primary platinum-based chemotherapy (P = 0.032). Also, p53 delta 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). p53 beta 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). Delta N'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. Oncogene (2010) 29, 1997-2004; doi:10.1038/onc.2009.482; published online 18 January 2010