BARD1 homozygous deletion, a possible alternative to BRCA1 mutation in basal breast cancer.
Hereditary breast cancers (BCs) are incompletely explained by BRCA genes abnormalities, as ∼70% of them are not associated with known genetic alterations. Array-based comparative genomic hybridization (aCGH) of tumors provides an opportunity for identifying new BC susceptibility genes. By analyzing our database of high-resolution aCGH profiles of 330 BCs, we identified a case with homozygous deletion of the entire BARD1 gene. The BARD1-deleted case displayed a familial history of BC and other clinico-pathological features of BRCAness, and a 17% probability of BRCA1/2 mutation. Analysis of constitutional DNA showed a BARD1 germline heterozygous deletion without BRCA1/2 mutation. Gene expression analysis using DNA microarrays classified the tumor as basal-like, with very low BARD1 and ID4 expression, but high expression of BRCA1, RAD51, PARP1, CHEK1, and FANCA. The tumor displayed a BRCA1-mutated expression profile. This is the first report of a non-BRCA1/2-mutated BC with somatic homozygous and germ-line heterozygous deletion of the entire BARD1 gene. This observation suggests that BARD1 might be a BC susceptibility gene that follows the Knudson rule. Identification of BARD1 deletion could have clinical applications including screening for hereditary forms. © 2010 Wiley-Liss, Inc.
Sabatier
Renaud
R
Department of Molecular Oncology, Centre de Recherche en Cancérologie de Marseille, INSERM/UMR891, Marseille, France.
Adélaïde
José
J
Finetti
Pascal
P
Ferrari
Anthony
A
Huiart
Laetitia
L
Sobol
Hagay
H
Chaffanet
Max
M
Birnbaum
Daniel
D
Bertucci
François
F
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D020869:Gene Expression Profiling; D019398:Genes, BRCA1; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D009154:Mutation; D018295:Neoplasms, Basal Cell / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases