TY - JOUR T1 - DNA methylation epigenotypes in breast cancer molecular subtypes. JF - Breast Cancer Res Y1 - 2010 A1 - Bediaga, Naiara G A1 - Acha-Sagredo, Amelia A1 - Guerra, Isabel A1 - Viguri, Amparo A1 - Albaina, Carmen A1 - Ruiz Diaz, Irune A1 - Rezola, Ricardo A1 - Alberdi, Maria Jesus A1 - Dopazo, Joaquin A1 - Montaner, David A1 - Renobales, Mertxe A1 - Fernandez, Agustin F A1 - Field, John K A1 - Fraga, Mario F A1 - Liloglou, Triantafillos A1 - de Pancorbo, Marian M KW - Aged KW - Breast Neoplasms KW - CpG Islands KW - DNA Methylation KW - Epigenesis, Genetic KW - Female KW - Gene Expression Profiling KW - Genes, p53 KW - Genotype KW - Humans KW - Ki-67 Antigen KW - Middle Aged KW - mutation KW - Neoplasm Grading KW - Oligonucleotide Array Sequence Analysis KW - Receptor, ErbB-2 KW - Tumor Suppressor Protein p53 AB -

INTRODUCTION: Identification of gene expression based breast cancer subtypes is considered as 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 there is only a limited understanding of the epigenetic mechanisms affected in those particular breast cancer subtypes. The present study was undertaken to dissect the breast cancer methylome and deliver specific epigenotypes associated with particular breast cancer subtypes.

METHODS: 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 biological 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. Using 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 identify novel subtype specific epigenotypes which 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 enables breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer.

VL - 12 IS - 5 U1 - https://www.ncbi.nlm.nih.gov/pubmed/20920229?dopt=Abstract ER -