PO-373 Methylation deregulation of miRNAs promoters in breast cancer in very young women

Introduction Breast cancer has the highest incidence rate of all cancers in women worldwide. Although early breast cancer generally has an excellent prognosis, breast cancer in young women is associated with a high risk of systemic disease at long-term follow-up. Epigenetic modifications were reported to play an important role in many disease onsets. MiRNAs not only function as a part of epigenetic machinery, but are also epigenetically modified by DNA methylation. The aim of the current study is to analyse the methylation alterations of CpG associated to miRNA encoding genes in breast cancer tumours occurring in very young women (BCVY) ( 45 years old). Material and methods We analysed DNAmethylation of 1264 genes encoding miRNAs in 26 BCVY samples and 15 samples from BCO using the ‘Illumina Infinium MethylationEPIC BeadChip’ array. Methylation differences were assessed using Wilcoxon Rank Sum test. Differences observed were validated using two independent populations: Flower et al 2015 and The Genome Caner Atlas (TCGA) methylation datasets. Expression of miRNAs regulated by CpG sites differently methylated were analysed in a meta-analysis using data from ClariomD array, miRNA expression published data from Pena-Chilet et al 2014 and TCGA gene expression data. We perform an expression validation study by real time-PCR of miRNAs differently methylated and expressed in BCVY comparing with older ones. Results and discussions We identified 193 significantly differently methylated CpG sites that were regulating genes encoding miRNAs. The hypomethylated CpGs were localised in islands and regions away from them (opensea) were mainly hypermethylated. We could validate a total of 10 methylation probes regulating miRNAs in the methylation validation data sets. Finally, the miRNAs mir-9–1, mir-184, mir-551b and mir-196a-1 were significantly differently methylated and de-regulated in BCVY in comparison with BCO Conclusion We identified a differential miRNA methylation profile in BCVY. Most of the miRNAs differently methylated between breast cancer age groups were previously described with aberrant methylation in cancer. Additionally, some of them presented significant different expression. The present study includes for the first time an analysis of methylation of miRNA encoding genes using the EPICarray in a large cohort of breast cancer samples occurring in young women. The four identified miRNAs with different methylation and expression in BCVY may be a promising epi/genetic biomarkers in BCVY risk.