title: High frequency of TP53 mutation in BRCA1 and sporadic basal-like carcinomas but not in BRCA1 luminal breast tumors.
abstract: 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 3 of 34 (9%), [corrected] 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.
authors.affiliation: Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Manié
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lehmann-Che
authors.forename: Gaelle
authors.initials: G
authors.lastname: Pierron
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Turpin
authors.forename: Mathilde
authors.initials: M
authors.lastname: Warcoin
authors.forename: Nadège
authors.initials: N
authors.lastname: Gruel
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lebigot
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Audrey
authors.initials: A
authors.lastname: Remenieras
authors.forename: Jean
authors.initials: J
authors.lastname: Feunteun
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Marc-Henri
authors.initials: MH
authors.lastname: Stern
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002280:Basal Cell Carcinoma / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D020125:Mutation, Missense