(E) Scheme used to combine CHIC-HS and MRS-HB classifications.
6 (D) EFS Kaplan-Meier plots of the same patients with HB classified following the CHIC-HS stratification (VL/L, Very Low and Low L, Low I, Intermediate H, High risk). (C) Multivariate Cox regression analysis comparing MRS with clinical CHIC-HS Stratification. Vertical line indicates 3-year EFS probability (in %). (B) EFS Kaplan-Meier plots of the same patients stratified according to the MRS-HB into 3 (left) or 4 (right) categories. Bottom, main genomic, pathologic and clinical features and their association with the MRS (right, Chi-Square test). Patient stratification was based on transcriptomic and epigenetic classifiers (right): 14q32-and 16+VIM-gene signatures and epigenomic Epi-CA/Epi-CB classification. (A) Top, representation of the MRS-HB categories for the 106 patients from which all biomarkers could be assessed. Molecular Risk Stratification of Hepatoblastoma (MRS-HB). Molecular features of HB and could be used to improve currentĬlinical stratification approaches and to develop treatments for Its inhibition in HB cell lines and patient-derived xenograftsĬonclusions: These findings provide a detailed insight into the Promising therapeutic target for intermediate and high-riskHBs, as Finally, we identified choline kinase alpha as a NFE2L2 mutations, a progenitor-like phenotype and clinicalĪggressiveness. MRS-3 category (28%), defined by strong 14q32 locus expressionĪnd Epi-CBmethylation features,was characterized by CTNNB1 and HB (MRS-HB), which encompasses 3 main prognostic categoriesĪnd improves the current clinical risk stratification approach. These findings, we defined the first molecular risk stratification of
OfDNA hypomethylation and CpGisland hypermethylation that areĪssociated with the C1/C2/C2B transcriptomic subtypes. By unsupervised analysis, we identifiedĢ epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees That includes hyperediting of the tumor suppressor BLCAPĬoncomitant with a genome-wide dysregulation of RNA editingĪnd the overexpression of mainly non-coding genes of the oncogenicġ4q32 DLK1-DIO3 locus. Results: We discovered a widespread epigenetic footprint of HB Methods: We performed a comprehensive genomic, transcriptomicĪnd epigenomic characterization of 159 clinicallyĪnnotated samples from 113 patients with HB, using highthroughput Targets in a move towards precision medicine for patients with Pathobiology and to identify new biomarkers and therapeutic Herein, we aimed to uncover the mechanisms of HB
With limited therapeutic options for patients with aggressive Nevertheless, it is the predominant pediatric liver cancer, Background & Aims: Hepatoblastoma (HB) is a rare disease.