Deregulated epigenetic mechanisms in sarcoma

Epigenetic mechanisms, such as DNA methylation, histone modifications, formation of superenhancers and enhancer hijacking can deregulate gene expression. Epigenetic changes have been shown to drive tumorigenesis and epigenetics-based drugs are being investigated to expand the therapeutic armamentarium against many cancers, including sarcoma. Our previous work (Chudasama et al. 2017) has unveiled the aberrant expression of sarcoma drivers, e.g. Fibroblast growth factor receptor 1 in multiple sarcoma subtypes. We are employing comprehensive epigenetic profiling methods such as ATAC-seq (chromatin accessibility), ACT-seq (histone modifications), EPIC-array (DNA methylation) and 4C-seq (three dimensional chromosomal confirmation) in sarcoma tumors and cell lines. Integrative analysis of these datasets coupled with genome and transcriptomes of sarcomas will reveal candidate aberrations, which will be pursued by in-depth functional investigations to identify mechanisms underlying overexpression of sarcoma drivers. These inquiries will identify entry points for targeted "epi-drugs" that may serve as single or combinatorial treatment options for sarcoma patients.

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