Next Article in Journal
Reading Cancer: Chromatin Readers as Druggable Targets for Cancer Treatment
Previous Article in Journal
Prognostic Factors for Advanced Pancreatic Cancer Treated with Gemcitabine Plus S-1: Retrospective Analysis and Development of a Prognostic Model
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle

Constitutive BRCA1 Promoter Hypermethylation Can Be a Predisposing Event in Isolated Early-Onset Breast Cancer

Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Department of Pathophysiology & Transplantation, Università degli Studi di Milano; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy
Unit of Bioinformatics and Biostatistics, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Immunohematology & Transfusion Medicine Service, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy
Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, 20142 Milano, Italy
Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
Author to whom correspondence should be addressed.
These authors equally contributed to the study.
Cancers 2019, 11(1), 58;
Received: 14 December 2018 / Accepted: 3 January 2019 / Published: 9 January 2019
PDF [1510 KB, uploaded 9 January 2019]


Early age at onset of breast cancer (eoBC) is suggestive of an increased genetic risk. Although genetic testing is offered to all eoBC-affected women, in isolated cases the detection rate of pathogenic variants is <10%. This study aimed at assessing the role of constitutive promoter methylation at BC-associated loci as an underlying predisposing event in women with eoBC and negative family history. Promoter methylation at 12 loci was assessed by the MassARRAY technology in blood from 154 BRCA1/2 negative patients with eoBC and negative family history, and 60 healthy controls. Hypermethylation was determined, within each promoter, by comparing the patient’s mean methylation value with thresholds based on one-sided 95% bootstrap confidence interval of the controls’ mean. Three patients had hypermethylated results, two at BRCA1 and one at RAD51C. Analyses on tumor tissue from the patient exceeding the highest threshold at BRCA1 revealed a mean methylation >60% and loss of heterozygosity at chromosome 17q. The patient hypermethylated at RAD51C showed low methylation in the tumor sample, ruling out a role for methylation-induced silencing in tumor development. In isolated eoBC patients, BRCA1 constitutive promoter methylation may be a predisposing event. Further studies are required to define the impact of methylation changes occurring at BC-predisposing genes and their role in tumorigenesis. View Full-Text
Keywords: breast cancer; epigenetics; BRCA1; promoter methylation breast cancer; epigenetics; BRCA1; promoter methylation

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Azzollini, J.; Pesenti, C.; Pizzamiglio, S.; Fontana, L.; Guarino, C.; Peissel, B.; Plebani, M.; Tabano, S.; Sirchia, S.M.; Colapietro, P.; Villa, R.; Paolini, B.; Verderio, P.; Miozzo, M.; Manoukian, S. Constitutive BRCA1 Promoter Hypermethylation Can Be a Predisposing Event in Isolated Early-Onset Breast Cancer. Cancers 2019, 11, 58.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top