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

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 perf...

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Autores principales: Felicio, Paula Silva, Melendez, Matias Eliseo, Arantes, Lidia Maria Rebolho Batista, Kerr, Ligia Maria, Carraro, Dirce Maria, Grasel, Rebeca Silveira, Campacci, Natalia, Scapulatempo-Neto, Cristovam, Fernandes, Gabriela Carvalho, de Carolina, Ana Carvalho, Palmero, Edenir Inêz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356847/
https://www.ncbi.nlm.nih.gov/pubmed/27926510
http://dx.doi.org/10.18632/oncotarget.13750
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author Felicio, Paula Silva
Melendez, Matias Eliseo
Arantes, Lidia Maria Rebolho Batista
Kerr, Ligia Maria
Carraro, Dirce Maria
Grasel, Rebeca Silveira
Campacci, Natalia
Scapulatempo-Neto, Cristovam
Fernandes, Gabriela Carvalho
de Carolina, Ana Carvalho
Palmero, Edenir Inêz
author_facet Felicio, Paula Silva
Melendez, Matias Eliseo
Arantes, Lidia Maria Rebolho Batista
Kerr, Ligia Maria
Carraro, Dirce Maria
Grasel, Rebeca Silveira
Campacci, Natalia
Scapulatempo-Neto, Cristovam
Fernandes, Gabriela Carvalho
de Carolina, Ana Carvalho
Palmero, Edenir Inêz
author_sort Felicio, Paula Silva
collection PubMed
description 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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spelling pubmed-53568472017-04-20 Genetic and epigenetic characterization of the BRCA1 gene in Brazilian women at-risk for hereditary breast cancer Felicio, Paula Silva Melendez, Matias Eliseo Arantes, Lidia Maria Rebolho Batista Kerr, Ligia Maria Carraro, Dirce Maria Grasel, Rebeca Silveira Campacci, Natalia Scapulatempo-Neto, Cristovam Fernandes, Gabriela Carvalho de Carolina, Ana Carvalho Palmero, Edenir Inêz Oncotarget Research Paper 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. Impact Journals LLC 2016-12-01 /pmc/articles/PMC5356847/ /pubmed/27926510 http://dx.doi.org/10.18632/oncotarget.13750 Text en Copyright: © 2017 Felicio et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Felicio, Paula Silva
Melendez, Matias Eliseo
Arantes, Lidia Maria Rebolho Batista
Kerr, Ligia Maria
Carraro, Dirce Maria
Grasel, Rebeca Silveira
Campacci, Natalia
Scapulatempo-Neto, Cristovam
Fernandes, Gabriela Carvalho
de Carolina, Ana Carvalho
Palmero, Edenir Inêz
Genetic and epigenetic characterization of the BRCA1 gene in Brazilian women at-risk for hereditary breast cancer
title Genetic and epigenetic characterization of the BRCA1 gene in Brazilian women at-risk for hereditary breast cancer
title_full Genetic and epigenetic characterization of the BRCA1 gene in Brazilian women at-risk for hereditary breast cancer
title_fullStr Genetic and epigenetic characterization of the BRCA1 gene in Brazilian women at-risk for hereditary breast cancer
title_full_unstemmed Genetic and epigenetic characterization of the BRCA1 gene in Brazilian women at-risk for hereditary breast cancer
title_short Genetic and epigenetic characterization of the BRCA1 gene in Brazilian women at-risk for hereditary breast cancer
title_sort genetic and epigenetic characterization of the brca1 gene in brazilian women at-risk for hereditary breast cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356847/
https://www.ncbi.nlm.nih.gov/pubmed/27926510
http://dx.doi.org/10.18632/oncotarget.13750
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