alexa BARD1 homozygous deletion, a possible alternative to BRCA1 mutation in basal breast cancer.
Molecular Biology

Molecular Biology

Journal of Cytology & Histology

Author(s): Sabatier R, Adlade J, Finetti P, Ferrari A, Huiart L,

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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. This article was published in Genes Chromosomes Cancer and referenced in Journal of Cytology & Histology

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