GSE100850 Epigenetic alterations detected in the genome of very young breast cancer patients: identification of new biomarkers

In this study we aimed to identify the key pathways that may cause cancer in this younger age group. EPIC and 450k Illumina methylation arrays were used to identify differences in DNA methylation in 74 breast cancer tumours, including 37 from very young women. Additionally, we analysed copy number variation (CNV) and DNAm age using methylation intensities from Illumina Infinium MethylationEPIC BeadChip.Although we are able to identify aberrant CNV patterns in breast cancer samples, they were not highly specific to BCVY. However, we identified 2 219 CpG sites that were differently methylated in BCVY vs. older women (false discovery rate< 0.05 beta-value difference ± 0.1), with the general hypomethylation profile affecting genes involved in neuronal-system pathways, cell communication, and extracellular matrix organisation, as confirmed by our experimental data. Additionally, a specific hypermethylation profile comprising 502 CpG sites located mainly in open- sea regions distinguished BCVY from older patients. Pathway enrichment analysis showed that regions implicated in the hypermethylation profile were involved in regulating genes related to Notch signalling pathways, the immune system, DNA repair, and vesicular trafficking. Moreover, BCVY presented ag e acceleration comparing with older women.The expression of genes regulated by differentially-methylated CpG sites was validated using both Cancer Genome Atlas genomic data and by qRT-PCR, the latter in an independent sample (...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by genome tiling array Homo sapiens Source Type: research