Human Gene Set: CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN


Standard name CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN
Systematic name M45034
Brief description Genes down-regulated in hepatoblastoma (HB) tumors as compared with non-tumor (NT) adjacent tissue.
Full description or abstract Background & Aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB.
Methods: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies.
Results: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth.
Conclusions: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 32240714   Authors: Carrillo-Reixach J,Torrens L,Simon-Coma M,Royo L,Domingo-Sàbat M,Abril-Fornaguera J,Akers N,Sala M,Ragull S,Arnal M,Villalmanzo N,Cairo S,Villanueva A,Kappler R,Garrido M,Guerra L,Sábado C,Guillén G,Mallo M,Piñeyro D,Vázquez-Vitali M,Kuchuk O,Mateos ME,Ramírez G,Santamaría ML,Mozo Y,Soriano A,Grotzer M,Branchereau S,de Andoin NG,López-Ibor B,López-Almaraz R,Salinas JA,Torres B,Hernández F,Uriz JJ,Fabre M,Blanco J,Paris C,Baj?iová V,Laureys G,Masnou H,Clos A,Belendez C,Guettier C,Sumoy L,Planas R,Jordà M,Nonell L,Czauderna P,Morland B,Sia D,Losic B,Buendia MA,Sarrias MR,Llovet JM,Armengol C
Exact source Supplementary Table 3: FDR<0.00001, FC<=-2
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External links https://www.sciencedirect.com/science/article/pii/S0168827820301872?via%3Dihub
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Source species Homo sapiens
Contributed by Carolina Armengol (Germans Trias i Pujol Research Institute (IGTP))
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identifier namespace		 Human_Ensembl_Gene_ID
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