Epigenetic control of the EWS‑FLI1 promoter in Ewing's sarcoma

Montoya,C.; Rey,L.; Rodríguez,J.; Fernández,M. J.; Troncoso,D.; Cañas,A.; Moreno,O.; Henríquez,B.; Rojas,A.

doi:10.3892/or.2020.7489

Epigenetic control of the EWS‑FLI1 promoter in Ewing's sarcoma

Authors:
- C. Montoya
- L. Rey
- J. Rodríguez
- M. J. Fernández
- D. Troncoso
- A. Cañas
- O. Moreno
- B. Henríquez
- A. Rojas
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Affiliations: Institute of Human Genetics, Faculty of Medicine, Pontificia Universidad Javeriana, Bogotá 110231, Colombia, Chile, Department of Pathology, Hospital Universitario San Ignacio, Bogotá 110231, Colombia, Chile, Department of Physiological Sciences, Faculty of Medicine, Pontificia Universidad Javeriana, Bogotá 110231, Colombia, Chile, Department of Internal Medicine, Hospital Universitario San Ignacio, Bogotá 110231, Colombia, Chile, Institute of Human Genetics, Faculty of Medicine, Pontificia Universidad Javeriana, Bogotá 110231, Colombia, Faculty of Medicine and Science, Universidad San Sebastián, Santiago 7510157, Chile
Published online on: February 5, 2020 https://doi.org/10.3892/or.2020.7489
Pages: 1199-1207
Copyright: © Montoya et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ewing sarcoma (ES) is a primary bone marrow tumor that very rarely develops in extra‑osseous tissues, such as lung. The hallmark of ES tumors is a translocation between chromosomes 11 and 22, resulting in a fusion protein, commonly referred to as EWS‑FLI1. The epigenetic profile (histone acetylation and methylation enrichment of the promoter region) that may regulate the expression of the aberrant transcription factor EWS‑FLI1, remains poorly studied and understood. Knowledge of epigenetic patterns associated with covalent histone modification and expression of enzymes associated with this process, can contribute to the understanding of the molecular basis of the disease, as well as to the identification of possible molecular targets involved in expression of the EWS‑FLI1 gene, so that therapeutic strategies may be improved in the future. In the present study, the transcriptional activation and repression of the EWS‑FLI1 fusion gene in ES was accompanied by selective deposition of histone markers on its promoter. The EWS‑FLI1 fusion gene was evaluated in two patients with ES using conventional cytogenetic, fluorescence in situ hybridization and nested PCR assays, which revealed that the aberrant expression of the EWS‑FLI1 gene is accompanied by enrichment of H3K4Me3, H3K9ac and H3K27ac at the promoter region.

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