title: BRCA1 haploinsufficiency leads to altered expression of genes involved in cellular proliferation and development.
abstract: The assessment of BRCA1 and BRCA2 coding sequences to identify pathogenic mutations associated with inherited breast/ovarian cancer syndrome has provided a method to identify high-risk individuals, allowing them to seek preventative treatments and strategies. However, the current test is expensive, and cannot differentiate between pathogenic variants and those that may be benign. Focusing only on one of the two BRCA partners, we have developed a biological assay for haploinsufficiency of BRCA1. Using a series of EBV-transformed cell lines, we explored gene expression patterns in cells that were BRCA1 wildtype compared to those that carried (heterozygous) BRCA1 pathogenic mutations. We identified a subset of 43 genes whose combined expression pattern is a sensitive predictor of BRCA1 status. The gene set was disproportionately made up of genes involved in cellular differentiation, lending credence to the hypothesis that single copy loss of BRCA1 function may impact differentiation, rendering cells more susceptible to undergoing malignant processes.
authors.affiliation: Departments of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada; Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
authors.forename: Harriet E
authors.initials: HE
authors.lastname: Feilotter
authors.affiliation: Departments of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada; Division of Cancer Biology and Genetics, Queen's University, Kingston, Ontario, Canada.
authors.forename: Claire
authors.initials: C
authors.lastname: Michel
authors.affiliation: Departments of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada; Division of Cancer Biology and Genetics, Queen's University, Kingston, Ontario, Canada.
authors.forename: Paolo
authors.initials: P
authors.lastname: Uy
authors.affiliation: Departments of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada; Division of Cancer Biology and Genetics, Queen's University, Kingston, Ontario, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Bathurst
authors.affiliation: Departments of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada; Departments of Biomedical and Molecular Sciences and Oncology, Queen's University, Kingston, Ontario, Canada; Division of Cancer Biology and Genetics, Queen's University, Kingston, Ontario, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Davey
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002472:Cell Transformation, Viral; D020869:Gene Expression Profiling; D019398:Genes, BRCA1; D015894:Genome, Human / Q000235:genetics; D057895:Haploinsufficiency; D004854:Herpesvirus 4, Human / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D007372:Interferons / Q000378:metabolism; D008214:Lymphocytes / Q000473:pathology / Q000821:virology; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D007372:Interferons