title: BARD1 homozygous deletion, a possible alternative to BRCA1 mutation in basal breast cancer.
abstract: 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.
authors.affiliation: Department of Molecular Oncology, Centre de Recherche en Cancérologie de Marseille, INSERM/UMR891, Marseille, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Sabatier
authors.forename: José
authors.initials: J
authors.lastname: Adélaïde
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Anthony
authors.initials: A
authors.lastname: Ferrari
authors.forename: Laetitia
authors.initials: L
authors.lastname: Huiart
authors.forename: Hagay
authors.initials: H
authors.lastname: Sobol
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
mesh_terms: 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*
chemical_list: D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases