Research Papers:

Genetic and epigenetic characterization of the BRCA1 gene in Brazilian women at-risk for hereditary breast cancer

Paula Silva Felicio, Matias Eliseo Melendez, Lidia Maria Rebolho Batista Arantes, Ligia Maria Kerr, Dirce Maria Carraro, Rebeca Silveira Grasel, Natalia Campacci, Cristovam Scapulatempo-Neto, Gabriela Carvalho Fernandes, Ana Carolina de Carvalho and Edenir Inêz Palmero _

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Oncotarget. 2017; 8:2850-2862. https://doi.org/10.18632/oncotarget.13750

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Paula Silva Felicio1, Matias Eliseo Melendez1, Lidia Maria Rebolho Batista Arantes1, Ligia Maria Kerr1,2, Dirce Maria Carraro3, Rebeca Silveira Grasel1, Natalia Campacci1, Cristovam Scapulatempo-Neto1,2, Gabriela Carvalho Fernandes1, Ana Carolina de Carvalho1, Edenir Inêz Palmero1

1 Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP, Brazil

2Department of Pathology, Barretos Cancer Hospital, Barretos, SP, Brazil

3International Research Center, AC Camargo Cancer Center, São Paulo, SP, Brazil

Correspondence to:

Edenir Inêz Palmero, email: [email protected]

Keywords: hereditary breast cancer, methylation, gene expression, breast cancer, BRCA1 gene

Received: August 16, 2016     Accepted: November 22, 2016     Published: December 01, 2016


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.

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