title: Loss of nuclear BRCA1 protein staining in normal tissue cells derived from BRCA1 and BRCA2 mutation carriers.
abstract: Enhanced genomic instability has been recently reported in normal cells derived from BRCA1/2 mutation carriers when placed in vitro in non-physiological stress conditions. We present here original data which help to explain the observed genomic instability. Leucocytes from BRCA1/2 mutation carriers, sporadic breast cancer patients and controls were prepared for BRCA1 immunocytochemistry. We show that BRCA1 containing nuclear dot like structures are detectable in about 80% of the leucocytes from controls and sporadic breast cancer patients, but are absent in the majority of normal cells from BRCA1 as well as BRCA2 mutation carriers (also in their normal breast cells). Our results thus indicate that the genomic instability observed in normal cells from BRCA1 and BRCA2 mutation carriers is associated with a down-regulation of nuclear BRCA1 protein accumulation in the dot like structures. These results suggest in addition that immunocytochemical or alternative molecular screening strategies might help to identify women with a high risk for breast (ovarian) cancer even when the underlying genetic defect remains undetectable.
authors: Laboratory of Molecular Oncology, Department of Medical Oncology, UZ Brussel, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors: Sylvia
authors: S
authors: De Brakeleer
authors: Marika
authors: M
authors: Bogdani
authors: Jacques
authors: J
authors: De Grève
authors: Julie
authors: J
authors: Decock
authors: Erica
authors: E
authors: Sermijn
authors: Maryse
authors: M
authors: Bonduelle
authors: Guido
authors: G
authors: Goelen
authors: Erik
authors: E
authors: Teugels
mesh_terms: D019313:BRCA1 Protein / Q000378:metabolism*; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D042822:Genomic Instability; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human