DNA methylation epigenotypes in breast cancer molecular subtypes

12 páginas, 3 figuras, 3 tablas.-- et al.[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.This work was supported by grants from project CGL2008-01131 (Departamento de Sanidad del Gobierno Vasco), S-PE08UN45 and PE09BF02 (Departamento de Ciencia y Tecnologia del Gobierno Vasco), BIO2008-04212, and RD06/0020/1019 (Red Tematica de Investigacion Cooperativa en Cancer, RTICC) from the MICINN. The CIBER de Enfermedades Raras is an initiative of the ISCIII. NGB had a doctoral fellowship from the Basque Government (Departamento de Educacion, Universidades e Investigacion).Peer reviewe

La investigación científica en el queso Idiazabal

Desde hace unos 15 años el queso Idiazabal ha sido objeto de una extensa investigación científica. Se describen algunos de los principales factores que inciden directamente en su calidad sensorial e higiénico-sanitaria, tanto durante el proceso de elaboración como durante los meses que dura la maduración. Entre estos factores destacamos el cuajo artesanal en pasta y la alimentación de las ovejas.Idiazabal gaztari buruzko zientzia-azterketa ugari egin izan dute azken 15 urteotan. Azterketa horiek agerian utzi dituzte gaztaren kalitatea eragiten duten eragileak, bai zentzumen-ezaugarrien aldetik baita higienearen eta osasunaren ikuspegitik ere, gazta egiteko prozesuan zein gazta heltzeko hilabeteetan zehar. Eragile horien artean, artisautza-gatzagia eta ardien elikadura azpimarratu ditzakegu.Depuis 15 ans, le fromage Idiazabal fait l'objet d'un vaste travail de recherche scientifique. Il comprend la description des principaux facteurs qui influent directement sur sa qualité sensorielle et hygièno-sanitaire, aussi bien durant le processus d'élaboration que pendant la période de maturation. Des facteurs tels que, notamment, la présure artisanale en pâte et l'alimentation des brebis.Idiazabal cheese has been extensively studied from a scientific perspective for the last 15 years. The present article describes some of the main factors that directly influence its sensory and hygienic quality, both during the fabrication process and during the ripening period. Among these factors the artisanally-prepared rennet and the role of grazing are considered