Distinct tumor protein p53 mutants in breast cancer subgroups. Issue 5 (1st September 2012)

• Record Type: Journal Article
• Authors: Dumay, Anne; Feugeas, Jean‐Paul; Wittmer, Evelyne; Lehmann‐Che, Jacqueline; Bertheau, Philippe; Espié, Marc; Plassa, Louis‐François; Cottu, Paul; Marty, Michel; André, Fabrice; Sotiriou, Christos; Pusztai, Lajos; de Thé, Hugues
• Is Part Of: International journal of cancer. Volume 132:Issue 5(2013:Mar. 01)
• Page Start: 1227
• Page End: 1231
• Publication Date: 2012-09-01
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.27767
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p> <italic>Tumor protein p53</italic> (<italic>TP53</italic>) 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 <italic>vs.</italic> 65%), notably A/T to G/C transitions (31 <italic>vs.</italic> 15%), whereas molecular apocrine and basal tumors presented much higher frequencies of complex mutations (deletions/insertions) (36 and 33%, respectively, <italic>vs.</italic> 18%). Accordingly, missense mutations were significantly more frequent in luminal tumors (75 <italic>vs.</italic> 54%), whereas basal tumors displayed significantly increased rates of <italic>TP53</italic> truncations (43 <italic>vs.</italic> 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 <italic>TP53</italic> alterations, but also to different functional consequences in the different breast cancer subtypes.</p> </abstract>