title: Distinct tumor protein p53 mutants in breast cancer subgroups.
abstract: Tumor protein p53 (TP53) is mutated in approximately 30% of breast cancers, but this frequency fluctuates widely between subclasses. We investigated the p53 mutation status in 572 breast tumors, classified into luminal, basal and molecular apocrine subgroups. As expected, the lowest mutation frequency was observed in luminal (26%), and the highest in basal (88%) tumors. Luminal tumors showed significantly higher frequency of substitutions (82 vs. 65%), notably A/T to G/C transitions (31 vs. 15%), whereas molecular apocrine and basal tumors presented much higher frequencies of complex mutations (deletions/insertions) (36 and 33%, respectively, vs. 18%). Accordingly, missense mutations were significantly more frequent in luminal tumors (75 vs. 54%), whereas basal tumors displayed significantly increased rates of TP53 truncations (43 vs. 25%), resulting in loss of function and/or expression. Interestingly, as basal tumors, molecular apocrine tumors presented with a high rate of complex mutations, but paradoxically, these were not associated with increased frequency of p53 truncation. As in luminal tumors, this could reflect a selective pressure for p53 gain of function, possibly through P63/P73 inactivation. Collectively, these observations point not only to different mechanisms of TP53 alterations, but also to different functional consequences in the different breast cancer subtypes.
authors.affiliation: Département de Biochimie, AP-HP, Hôpital Saint-Louis, Institut Universitaire d'Hématologie, CNRS UMR7212/INSERM U944/University Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Dumay
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Feugeas
authors.forename: Evelyne
authors.initials: E
authors.lastname: Wittmer
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lehmann-Che
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertheau
authors.forename: Marc
authors.initials: M
authors.lastname: Espié
authors.forename: Louis-François
authors.initials: LF
authors.lastname: Plassa
authors.forename: Paul
authors.initials: P
authors.lastname: Cottu
authors.forename: Michel
authors.initials: M
authors.lastname: Marty
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C495901:TP53 protein, human; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins