title: Alternative splicing of p53 and p73: the novel p53 splice variant p53delta is an independent prognostic marker in ovarian cancer.
abstract: 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.
authors.affiliation: Department of Gynecology and Obstetrics, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Hofstetter
authors.forename: A
authors.initials: A
authors.lastname: Berger
authors.forename: H
authors.initials: H
authors.lastname: Fiegl
authors.forename: N
authors.initials: N
authors.lastname: Slade
authors.forename: A
authors.initials: A
authors.lastname: Zorić
authors.forename: B
authors.initials: B
authors.lastname: Holzer
authors.forename: E
authors.initials: E
authors.lastname: Schuster
authors.forename: V J
authors.initials: VJ
authors.lastname: Mobus
authors.forename: D
authors.initials: D
authors.lastname: Reimer
authors.forename: G
authors.initials: G
authors.lastname: Daxenbichler
authors.forename: C
authors.initials: C
authors.lastname: Marth
authors.forename: A G
authors.initials: AG
authors.lastname: Zeimet
authors.forename: N
authors.initials: N
authors.lastname: Concin
authors.forename: R
authors.initials: R
authors.lastname: Zeillinger
mesh_terms: D017398:Alternative Splicing; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007438:Introns; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins