High frequency of TP53 mutation in BRCA1 and sporadic basal-like carcinomas but not in BRCA1 luminal breast tumors.
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.
Manié
Elodie
E
Institut Curie, Centre de Recherche, Paris, France.
Vincent-Salomon
Anne
A
Lehmann-Che
Jacqueline
J
Pierron
Gaelle
G
Turpin
Elisabeth
E
Warcoin
Mathilde
M
Gruel
Nadège
N
Lebigot
Ingrid
I
Sastre-Garau
Xavier
X
Lidereau
Rosette
R
Remenieras
Audrey
A
Feunteun
Jean
J
Delattre
Olivier
O
de Thé
Hugues
H
Stoppa-Lyonnet
Dominique
D
Stern
Marc-Henri
MH
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