title: Genetic and epigenetic characterization of the BRCA1 gene in Brazilian women at-risk for hereditary breast cancer.
abstract: This study aimed to characterize women at-risk for hereditary BC regarding their clinical and molecular characteristics (mutation and methylation in the BRCA1 gene) and correlate the gene expression levels with histopathological, clinical and family history information. BRCA1 real time qPCR was performed to evaluate methylation status and gene expression. The study included 88 women grouped according to the BRCA1 mutational status: 23 BRCA1 mutated, 22 with a Variant of Unknown Significance (VUS) in BRCA1 and 43 BRCA1 WT. Most BRCA1 mutated tumors were triple negative (69.6%) and had histologic grade III (61.0%). Patients with VUS/WT BRCA1 were predominantly of luminal B subtype with histological grades I and II. Regarding the methylation profile, BRCA1 hypermethylation was observed in only two patients (both WT) and none had association with pathogenic BRCA1 mutation. In one patient methylation was present in both, tumor and normal tissues. Hypermethylated tumors had ductal histology, negativity for ER and occurred in < 50 years patients. Gene expression profile showed in all groups lower BRCA1 mRNA levels in tumor tissue compared to the adjacent breast tissue, thereby indicating the loss/decrease of gene function. No association was found between the levels of BRCA1 gene expression and family history of cancer. In summary, our findings suggested that methylation at the BRCA1 gene is not the "second" event in the development of BC in patients with germline mutations in BRCA1 and, although rare, BRCA1 epimutations can constitute an explanation for a fraction of HBOC families.
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Paula Silva
authors.initials: PS
authors.lastname: Felicio
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Matias Eliseo
authors.initials: ME
authors.lastname: Melendez
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Lidia Maria Rebolho Batista
authors.initials: LM
authors.lastname: Arantes
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.|Department of Pathology, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Ligia Maria
authors.initials: LM
authors.lastname: Kerr
authors.affiliation: International Research Center, AC Camargo Cancer Center, São Paulo, SP, Brazil.
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Rebeca Silveira
authors.initials: RS
authors.lastname: Grasel
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Natalia
authors.initials: N
authors.lastname: Campacci
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.|Department of Pathology, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo-Neto
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Gabriela Carvalho
authors.initials: GC
authors.lastname: Fernandes
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Carvalho
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil.
authors.forename: Edenir Inêz
authors.initials: EI
authors.lastname: Palmero
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor; D001938:Brazil; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012306:Risk; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor
keywords: BRCA1 gene; breast cancer; gene expression; hereditary breast cancer; methylation