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Breast Cancer Research
Published in: Breast Cancer Research 5/2010

Open Access 01-10-2010 | Research article

DNA methylation epigenotypes in breast cancer molecular subtypes

Authors: Naiara G Bediaga, Amelia Acha-Sagredo, Isabel Guerra, Amparo Viguri, Carmen Albaina, Irune Ruiz Diaz, Ricardo Rezola, María Jesus Alberdi, Joaquín Dopazo, David Montaner, Mertxe de Renobales, Agustín F Fernández, John K Field, Mario F Fraga, Triantafillos Liloglou, Marian M de Pancorbo

Published in: Breast Cancer Research | Issue 5/2010

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Abstract

Introduction

Identification of gene expression-based breast cancer subtypes is considered a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene-expression changes occurring in breast cancer. So far, these epigenetic contributions to sporadic breast cancer subtypes have not been well characterized, and only a limited understanding exists of the epigenetic mechanisms affected in those particular breast cancer subtypes. The present study was undertaken to dissect the breast cancer methylome and to deliver specific epigenotypes associated with particular breast cancer subtypes.

Methods

By using a microarray approach, we analyzed DNA methylation in regulatory regions of 806 cancer-related genes in 28 breast cancer paired samples. We subsequently performed substantial technical and biologic validation by pyrosequencing, investigating the top qualifying 19 CpG regions in independent cohorts encompassing 47 basal-like, 44 ERBB2+ overexpressing, 48 luminal A, and 48 luminal B paired breast cancer/adjacent tissues. With the all-subset selection method, we identified the most subtype-predictive methylation profiles in multivariable logistic regression analysis.

Results

The approach efficiently recognized 15 individual CpG loci differentially methylated in breast cancer tumor subtypes. We further identified novel subtype-specific epigenotypes that clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors.

Conclusions

Our results provide evidence that well-defined DNA methylation profiles enable breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer.
Appendix
Available only for authorised users
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Metadata
Title
DNA methylation epigenotypes in breast cancer molecular subtypes
Authors
Naiara G Bediaga
Amelia Acha-Sagredo
Isabel Guerra
Amparo Viguri
Carmen Albaina
Irune Ruiz Diaz
Ricardo Rezola
María Jesus Alberdi
Joaquín Dopazo
David Montaner
Mertxe de Renobales
Agustín F Fernández
John K Field
Mario F Fraga
Triantafillos Liloglou
Marian M de Pancorbo
Publication date
01-10-2010
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2010
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2721

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