title: No evidence for breast cancer susceptibility associated with variants of BRD7, a component of p53 and BRCA1 pathways.
abstract: BRD7 (bromodomain 7), a subunit of poly-bromo-associated BRG1-associated factor (PBAF)-specific Swi/Snf chromatin remodeling complexes, has been proposed as a tumour suppressor protein following its identification as an important component of both functional p53 and BRCA1 (breast cancer 1, early onset) pathways. As low BRD7 expression levels have been linked to p53-wild-type breast tumour cells, we hypothesized an implication of BRD7 germline alterations in the pathogenesis of hereditary breast cancer similar to that of TP53 in Li-Fraumeni syndrome. We performed sequence analysis of the BRD7 gene on 61 high-risk individuals with hereditary or very-early-onset breast cancer and 100 healthy controls. Four potentially disease-causing single-nucleotide alterations were detected within the cohort of breast cancer patients (one listed as a rare single-nucleotide polymorphism (SNP) in the NCBI (National Center for Biotechnology Information) SNP database). Two of the detected variants were also each found once within the control collective. Segregation analysis on both families of those carrying the remaining two variants revealed segregation of these BRD7 alterations independent of breast cancer. In conclusion, it seems that the BRD7 variants we detected represent rare polymorphisms and mainly rule out BRD7 as a frequent high-penetrance breast cancer susceptibility gene. However, further analyses in larger cohorts of women with hereditary breast cancer should clarify the role of BRD7 in breast cancer predisposition.
authors.affiliation: Institute of Cell and Molecular Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Penkert
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Doris
authors.initials: D
authors.lastname: Steinemann
authors.forename: Dorothea
authors.initials: D
authors.lastname: Gadzicki
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult; D000092468:Bromodomain Containing Proteins
chemical_list: D019313:BRCA1 Protein; D002868:Chromosomal Proteins, Non-Histone; D016159:Tumor Suppressor Protein p53; C492913:BRCA1 protein, human; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins; C495901:TP53 protein, human