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Abstract
Sarcomas comprise a large number of rare, histogenetically heterogeneous, mesenchymal tumors. Cancers such as Ewing‘s sarcoma, liposarcoma, rhabdomyosarcoma and synovial sarcoma can be generated by the transduction of mesenchymal stem cell progenitors with sarcoma-pathognomonic oncogenic fusions, a neoplastic transformation process accompanied by profound locus-specific and pangenomic epigenetic alterations. The epigenetic activities of histone-modifying and chromatin-remodeling enzymes such as SUV39H1/KMT1A, EZH2/KMT6A and BMI1 are central to epigenetic-regulated transformation, a property we coin oncoepigenic. Sarcoma-specific oncoepigenic aberrations modulate critical signaling pathways that control cell growth and differentiation including several miRNAs, Wnt, PI3K/AKT, Sav-RASSF1-Hpo and regulators of the G1 and G2/M checkpoints of the cell cycle. Herein an overview of the current knowledge of this rapidly evolving field that will undoubtedly uncover additional oncoepigenic mechanisms and yield druggable targets in the near future is discussed.
Acknowledgements
The author wishes to thank Summer Bennani-Baiti for being an important source of inspiration, and is in debt to Barbara Bennani-Baiti for discussions and critical reading of the manuscript.
Financial&competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.