title: BRCA1-related gene signature in breast cancer: the role of ER status and molecular type.
abstract: There is an ongoing debate whether hereditary breast cancer is a clinical entity distinct from sporadic breast cancer. We tried to shed some light on this issue by comparing the molecular profiles of these two types of cancer using DNA microarrays. Our results show that a previously reported marked difference between BRCA1-mutation linked and sporadic breast cancer was probably due to uneven stratification of samples with different ER status and basal-like versus luminal-like subtype. We observed that apparent difference between BRCA1-linked and other types of breast cancer found in univariate analysis was diminished when data were corrected for ER status and molecular subtype in multivariate analyses. In fact, the difference in gene expression pattern of BRCA1-mutated and sporadic cancer is very discrete. These conclusions were supported by the results of Q-PCR validation. We also found that BRCA1 promoter hypermethylation had similar effect on global gene expression as mutation-induced protein truncation. Thus, in the molecular studies of hereditary breast cancer, BRCA1 promoter methylation should be recognized and considered together with gene mutation.
authors.affiliation: Department of Tumor Biology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland. kasial@io.gliwice.pl
authors.forename: Katarzyna Marta
authors.initials: KM
authors.lastname: Lisowska
authors.forename: Volha
authors.initials: V
authors.lastname: Dudaladava
authors.forename: Michal
authors.initials: M
authors.lastname: Jarzab
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Ewa
authors.initials: E
authors.lastname: Chmielik
authors.forename: Ewa
authors.initials: E
authors.lastname: Stobiecka
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Barbara
authors.initials: B
authors.lastname: Jarzab
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019313:BRCA1 Protein