Cargando…

Analysis of BRCA1 and RAD51C Promoter Methylation in Italian Families at High-Risk of Breast and Ovarian Cancer

Previous studies on breast and ovarian carcinoma (BC and OC) revealed constitutional BRCA1 and RAD51C promoter hypermethylation as epigenetic alterations leading to tumor predisposition. Nevertheless, the impact of epimutations at these genes is still debated. One hundred and eight women affected by...

Descripción completa

Detalles Bibliográficos
Autores principales: Tabano, Silvia, Azzollini, Jacopo, Pesenti, Chiara, Lovati, Sara, Costanza, Jole, Fontana, Laura, Peissel, Bernard, Miozzo, Monica, Manoukian, Siranoush
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226593/
https://www.ncbi.nlm.nih.gov/pubmed/32276467
http://dx.doi.org/10.3390/cancers12040910
_version_ 1783534325072920576
author Tabano, Silvia
Azzollini, Jacopo
Pesenti, Chiara
Lovati, Sara
Costanza, Jole
Fontana, Laura
Peissel, Bernard
Miozzo, Monica
Manoukian, Siranoush
author_facet Tabano, Silvia
Azzollini, Jacopo
Pesenti, Chiara
Lovati, Sara
Costanza, Jole
Fontana, Laura
Peissel, Bernard
Miozzo, Monica
Manoukian, Siranoush
author_sort Tabano, Silvia
collection PubMed
description Previous studies on breast and ovarian carcinoma (BC and OC) revealed constitutional BRCA1 and RAD51C promoter hypermethylation as epigenetic alterations leading to tumor predisposition. Nevertheless, the impact of epimutations at these genes is still debated. One hundred and eight women affected by BC, OC, or both and considered at very high risk of carrying BRCA1 germline mutations were studied. All samples were negative for pathogenic variants or variants of uncertain significance at BRCA testing. Quantitative BRCA1 and RAD51C promoter methylation analyses were performed by Epityper mass spectrometry on peripheral blood samples and results were compared with those in controls. All the 108 analyzed cases showed methylation levels at the BRCA1/RAD51C promoter comparable with controls. Mean methylation levels (± stdev) at the BRCA1 promoter were 4.3% (± 1.4%) and 4.4% (± 1.4%) in controls and patients, respectively (p > 0.05; t-test); mean methylation levels (± stdev) at the RAD51C promoter were 4.3% (± 0.9%) and 3.7% (± 0.9%) in controls and patients, respectively (p > 0.05; t-test). Based on these observations; the analysis of constitutional methylation at promoters of these genes does not seem to substantially improve the definition of cancer risks in patients. These data support the idea that epimutations represent a very rare event in high-risk BC/OC populations.
format Online
Article
Text
id pubmed-7226593
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72265932020-05-18 Analysis of BRCA1 and RAD51C Promoter Methylation in Italian Families at High-Risk of Breast and Ovarian Cancer Tabano, Silvia Azzollini, Jacopo Pesenti, Chiara Lovati, Sara Costanza, Jole Fontana, Laura Peissel, Bernard Miozzo, Monica Manoukian, Siranoush Cancers (Basel) Article Previous studies on breast and ovarian carcinoma (BC and OC) revealed constitutional BRCA1 and RAD51C promoter hypermethylation as epigenetic alterations leading to tumor predisposition. Nevertheless, the impact of epimutations at these genes is still debated. One hundred and eight women affected by BC, OC, or both and considered at very high risk of carrying BRCA1 germline mutations were studied. All samples were negative for pathogenic variants or variants of uncertain significance at BRCA testing. Quantitative BRCA1 and RAD51C promoter methylation analyses were performed by Epityper mass spectrometry on peripheral blood samples and results were compared with those in controls. All the 108 analyzed cases showed methylation levels at the BRCA1/RAD51C promoter comparable with controls. Mean methylation levels (± stdev) at the BRCA1 promoter were 4.3% (± 1.4%) and 4.4% (± 1.4%) in controls and patients, respectively (p > 0.05; t-test); mean methylation levels (± stdev) at the RAD51C promoter were 4.3% (± 0.9%) and 3.7% (± 0.9%) in controls and patients, respectively (p > 0.05; t-test). Based on these observations; the analysis of constitutional methylation at promoters of these genes does not seem to substantially improve the definition of cancer risks in patients. These data support the idea that epimutations represent a very rare event in high-risk BC/OC populations. MDPI 2020-04-08 /pmc/articles/PMC7226593/ /pubmed/32276467 http://dx.doi.org/10.3390/cancers12040910 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tabano, Silvia
Azzollini, Jacopo
Pesenti, Chiara
Lovati, Sara
Costanza, Jole
Fontana, Laura
Peissel, Bernard
Miozzo, Monica
Manoukian, Siranoush
Analysis of BRCA1 and RAD51C Promoter Methylation in Italian Families at High-Risk of Breast and Ovarian Cancer
title Analysis of BRCA1 and RAD51C Promoter Methylation in Italian Families at High-Risk of Breast and Ovarian Cancer
title_full Analysis of BRCA1 and RAD51C Promoter Methylation in Italian Families at High-Risk of Breast and Ovarian Cancer
title_fullStr Analysis of BRCA1 and RAD51C Promoter Methylation in Italian Families at High-Risk of Breast and Ovarian Cancer
title_full_unstemmed Analysis of BRCA1 and RAD51C Promoter Methylation in Italian Families at High-Risk of Breast and Ovarian Cancer
title_short Analysis of BRCA1 and RAD51C Promoter Methylation in Italian Families at High-Risk of Breast and Ovarian Cancer
title_sort analysis of brca1 and rad51c promoter methylation in italian families at high-risk of breast and ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226593/
https://www.ncbi.nlm.nih.gov/pubmed/32276467
http://dx.doi.org/10.3390/cancers12040910
work_keys_str_mv AT tabanosilvia analysisofbrca1andrad51cpromotermethylationinitalianfamiliesathighriskofbreastandovariancancer
AT azzollinijacopo analysisofbrca1andrad51cpromotermethylationinitalianfamiliesathighriskofbreastandovariancancer
AT pesentichiara analysisofbrca1andrad51cpromotermethylationinitalianfamiliesathighriskofbreastandovariancancer
AT lovatisara analysisofbrca1andrad51cpromotermethylationinitalianfamiliesathighriskofbreastandovariancancer
AT costanzajole analysisofbrca1andrad51cpromotermethylationinitalianfamiliesathighriskofbreastandovariancancer
AT fontanalaura analysisofbrca1andrad51cpromotermethylationinitalianfamiliesathighriskofbreastandovariancancer
AT peisselbernard analysisofbrca1andrad51cpromotermethylationinitalianfamiliesathighriskofbreastandovariancancer
AT miozzomonica analysisofbrca1andrad51cpromotermethylationinitalianfamiliesathighriskofbreastandovariancancer
AT manoukiansiranoush analysisofbrca1andrad51cpromotermethylationinitalianfamiliesathighriskofbreastandovariancancer