03411nas a2200529 4500008004100000022001400041245007000055210006900125260000900194300000800203490000700211520186600218653000902084653002102093653001602114653002002130653002402150653001102174653003002185653001502215653001302230653001102243653001802254653001602272653001302288653002102301653004402322653002102366653003302387100002302420700002502443700001902468700001902487700002002506700002202526700002002548700002602568700002002594700002002614700002202634700002602656700001902682700002002701700002802721700002702749856010502776 2010 eng d a1465-542X00aDNA methylation epigenotypes in breast cancer molecular subtypes.0 aDNA methylation epigenotypes in breast cancer molecular subtypes c2010 aR770 v123 a
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.
10aAged10aBreast Neoplasms10aCpG Islands10aDNA Methylation10aEpigenesis, Genetic10aFemale10aGene Expression Profiling10aGenes, p5310aGenotype10aHumans10aKi-67 Antigen10aMiddle Aged10amutation10aNeoplasm Grading10aOligonucleotide Array Sequence Analysis10aReceptor, ErbB-210aTumor Suppressor Protein p531 aBediaga, Naiara, G1 aAcha-Sagredo, Amelia1 aGuerra, Isabel1 aViguri, Amparo1 aAlbaina, Carmen1 aDiaz, Irune, Ruiz1 aRezola, Ricardo1 aAlberdi, Maria, Jesus1 aDopazo, Joaquin1 aMontaner, David1 aRenobales, Mertxe1 aFernandez, Agustin, F1 aField, John, K1 aFraga, Mario, F1 aLiloglou, Triantafillos1 ade Pancorbo, Marian, M uhttps://www.clinbioinfosspa.es/content/dna-methylation-epigenotypes-breast-cancer-molecular-subtypes