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Identification and Experimental Validation of Druggable Epigenetic Targets in Hepatoblastoma by Alex Clavería-Cabello; Jose Maria Herranz; Maria Ujue Latasa; Maria Arechederra; Iker Uriarte; Antonio Pineda-Lucena; Felipe Prosper; Pedro Berraondo; Cristina Alonso; Bruno Sangro; Jose Juan García Marin; Maria Luz Martinez-Chantar; Sergio Ciordia; Fernando José Corrales; Paola Francalanci; Rita Alaggio; Jessica Zucman-Rossi; Emilie Indersie; Stefano Cairo; Montserrat Domingo-Sàbat; Laura Zanatto; Pau Sancho-Bru; Carolina Armengol; Carmen Berasain; Maite García Fernandez-Barrena; Matias Antonio Avila is a Medicine article available to read on EtoBox.
What is Identification and Experimental Validation of Druggable Epigenetic Targets in Hepatoblastoma about?
Background & Aims Hepatoblastoma (HB) is the most frequent childhood liver cancer. Patients with aggressive tumors have limited therapeutic options; therefore, a better understanding of HB pathogenesis is needed to improve treatment. HB have a very low mutational burden; however, epigenetic alterations are increasingly recognized. We aimed to identify epigenetic regulators consistently dysregulated in HB and to evaluate the therapeutic efficacy of their targeting in clinically relevant models. Methods We performed a comprehensive transcriptomic analysis of 180 epigenetic genes. Data from fetal, pediatric, adult, peritumoral (n=72) and tumoral (n=91) tissues were integrated. Selected epigenetic drugs were tested in HB cells. The most relevant epigenetic target identified was validated in primary HB cells, HB organoids, a PDX model, and a genetic mouse model. Transcriptomic, proteomic and metabolomic mechanistic analyses were implemented. Results Altered expression of genes regulating DNA methylation and histones modifications was consistently observed in association with molecular and clinical features of poor prognosis. The histone methyl-transferase G9a was markedly upregulated in
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- Author
- Alex Clavería-Cabello; Jose Maria Herranz; Maria Ujue Latasa; Maria Arechederra; Iker Uriarte; Antonio Pineda-Lucena; Felipe Prosper; Pedro Berraondo; Cristina Alonso; Bruno Sangro; Jose Juan García Marin; Maria Luz Martinez-Chantar; Sergio Ciordia; Fernando José Corrales; Paola Francalanci; Rita Alaggio; Jessica Zucman-Rossi; Emilie Indersie; Stefano Cairo; Montserrat Domingo-Sàbat; Laura Zanatto; Pau Sancho-Bru; Carolina Armengol; Carmen Berasain; Maite García Fernandez-Barrena; Matias Antonio Avila
- Publisher
- Elsevier BV
- Published
- 2023
- Language
- EN
- Field
- Medicine (Health Sciences)