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High Frequency of TP53 Mutation in BRCA1 and Sporadic Basal-like Carcinomas but not in BRCA1 Luminal Breast Tumors

¹ Institut Curie, Centre de Recherche; ² Institut National de la Sante et de la Recherche Medicale U830; ³ Institut Curie, Department of Tumor Biology; ⁴ Department of Biochemistry, Hopital Saint-Louis APHP; ⁵ Centre National de la Recherche Scientifique UMR 7151, University Hematology Institute, University Paris 7 Denis Diderot; ⁶ Institut Curie, Translational Research Department; ⁷ University Paris Descartes, Paris, France; ⁸ Institut National de la Sante et de la Recherche Medicale, U735, Centre René Huguenin, Saint-Cloud, France; and ⁹ Institut Gustave Roussy and ¹⁰ Centre National de la Recherche Scientifique-University Paris XI FRE#2939, Villejuif, France

Requests for reprints: Marc-Henri Stern, Institut Curie, Centre de Recherche, 26 rue d'Ulm, Paris 75248, France. Phone: 33-1-56-24-66-46; Fax: 33-1-56-24-66-30; E-mail: marc-henri.stern{at}curie.fr.

Key Words: BRCA1 • breast carcinoma • TP53

Breast tumors with a germ-line mutation of BRCA1 (BRCA1 tumors) and basal-like carcinoma (BLC) are associated with a high rate of TP53 mutation. Because BRCA1 tumors frequently display a basal-like phenotype, this study was designed to determine whether TP53 mutations are correlated with the hereditary BRCA1 mutated status or the particular phenotype of these tumors. The TP53 gene status was first investigated in a series of 35 BRCA1 BLCs using immunohistochemistry, direct sequencing of the coding sequence, and functional analysis of separated alleles in yeast, and compared with the TP53 status in a series of 38 sporadic (nonhereditary) BLCs. Using this sensitive approach, TP53 was found to be frequently mutated in both BRCA1 (34 of 35, 97%) and sporadic (35 of 38, 92%) BLCs. However, the spectrum of mutation was different, particularly with a higher rate of complex mutations, such as insertion/deletion, in BRCA1 BLCs than in the sporadic group [14 of 33 (42%) and 13 of 34 (9%), respectively; P = 0.002]. Secondly, the incidence of TP53 mutations was analyzed in 19 BRCA1 luminal tumors using the same strategy. Interestingly, only 10 of these 19 tumors were mutated (53%), a frequency similar to that found in grade-matched sporadic luminal tumors. In conclusion, TP53 mutation is highly recurrent in BLCs independently of BRCA1 status, but not a common feature of BRCA1 luminal tumors. [Cancer Res 2009;69(2):663–71]

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				Correction: Article on TP53 in BRCA1 Breast Tumors Cancer Res., April 1, 2009; 69(7): 3240 - 3240. [Full Text] [PDF]