Cancer is a genetic as well an epigenetic disease. A prominent epigenetic alteration is DNA-methylation in the promoter region of the gene that prevents the gene to be expressed. Recently high-throughput methods to analyze the methylation status of genes in a large number of samples simultaneously have been developed. Now, even global DNA-methylation can be studied using stable tumor DNA preparations, rather than the labile RNA preparations required for cDNA microarray analyses. This way, new target genes, which provide the basis to improve treatment strategies, can be discovered. With the aim to catch up with the current genomic information and to implement the epigenetic DNA-methylation analyses in the clinical setting, we formed the present consortium encompassing members of the European Union and associated member states to take a multidisciplinary and innovative approach to study DNA-methylation of breast tumors in order to improve prognosis and treatment possibilities of the patients. The participating centers contribute complementary state-of-the-art proprietary technical expertise, large and well-documented tissue resources, and intense clinical expertise. Recently, members of this consortium have developed epigenetic predictive signatures for breast cancer patients treated with endocrine therapy. This proof-of-principle is the basis for the breast cancer studies proposed in the present project and the main objectives are: 1) By genome-wide DNA-methylation screening identify new therapeutic targets. 2) Develop prognostic and predictive DNA-methylation markers. 3) Confirm these findings at the mRNA and protein level, and in clinically relevant subgroups of breast cancer. 4) Commercialize relevant target genes discovered for prognostic, predictive and therapeutic use. Achievements expected are the improvement of patient prognosis by development of better therapeutic approaches based on new targeted therapies and better therapy selection.
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Funding SchemeSTREP - Specific Targeted Research Project