In this episode of the Epigenetics Podcast, we caught up with Eleni Tomazou from St. Anna Children's Cancer Research Institute in Vienna to talk about her work on Epigenome-based precision medicine.
The Tomazou lab studies Ewing sarcoma and the effects of Epigenetic factors on this disease. Ewing sarcoma is a type of cancer that affects bone and soft tissue of children and young adults, with a peak incidence at the age of 15. Ewing sarcoma is among the pediatric cancer types with the lowest survival rates and the development of novel therapies was obstructed by the limited understanding of the mechanisms behind the disease.
Work done in Eleni Tomazou's group identified an epigenetic signature of Ewing sarcoma which, ultimately, lead to the possibility to diagnose Ewing sarcoma from liquid biopsies. The team is now looking to find actionable targets like enhancers to develop therapies, finding biomarkers to enable disease monitoring, and to further characterize these tumors to decipher intra-tumor epigenetic heterogeneity and characterize the developmental stage of the cell of origin.
References
Tomazou, E. M., Sheffield, N. C., Schmidl, C., Schuster, M., Schönegger, A., Datlinger, P., Kubicek, S., Bock, C., & Kovar, H. (2015). Epigenome Mapping Reveals Distinct Modes of Gene Regulation and Widespread Enhancer Reprogramming by the Oncogenic Fusion Protein EWS-FLI1. Cell Reports, 10(7), 1082–1095. https://doi.org/10.1016/j.celrep.2015.01.042
Sheffield, N. C., Pierron, G., Klughammer, J., Datlinger, P., Schönegger, A., Schuster, M., Hadler, J., Surdez, D., Guillemot, D., Lapouble, E., Freneaux, P., Champigneulle, J., Bouvier, R., Walder, D., Ambros, I. M., Hutter, C., Sorz, E., Amaral, A. T., de Álava, E., … Tomazou, E. M. (2017). DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma. Nature Medicine, 23(3), 386–395. https://doi.org/10.1038/nm.4273
Terlecki-Zaniewicz, S., Humer, T., Eder, T., Schmoellerl, J., Heyes, E., Manhart, G., Kuchynka, N., Parapatics, K., Liberante, F. G., Müller, A. C., Tomazou, E. M., & Grebien, F. (2021). Biomolecular condensation of NUP98 fusion proteins drives leukemogenic gene expression. Nature Structural & Molecular Biology, 28(2), 190–201. https://doi.org/10.1038/s41594-020-00550-w
Peneder, P., Stütz, A. M., Surdez, D., Krumbholz, M., Semper, S., Chicard, M., Sheffield, N. C., Pierron, G., Lapouble, E., Tötzl, M., Ergüner, B., Barreca, D., Rendeiro, A. F., Agaimy, A., Boztug, H., Engstler, G., Dworzak, M., Bernkopf, M., Taschner-Mandl, S., … Tomazou, E. M. (2021). Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden. Nature Communications, 12(1), 3230. https://doi.org/10.1038/s41467-021-23445-w
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