Epigenetic footprint of hepatoblastoma defines a novel integrative molecular classification with clinical implications [HTA-2_0]. Epigenetic footprint of hepatoblastoma defines a novel integrative molecular classification with clinical implications [HTA-2_0]

Hepatoblastoma (HB) is the predominant pediatric liver cancer with limited therapeutic options for patients with aggressive tumors. Nevertheless, it is a rare disease. Here, we performed a high-throughput molecular study of 32 patients with HB and major findings were validated in additional 80 cases. We unveiled an epigenetic footprint including downregulation of RNA-editing, hyperediting of the tumor suppressor BLCAP,14q32 DLK1-DIO3 locus overexpression, DNA hypomethylation and CpG island hypermethylation. Based on these findings, we defined an integrative molecular classification of HB that improve current clinical stratification, and identified CHKA as a therapeutic target for the poor prognostic subclass. Overall design: 52 samples profiled from 32 patients with Hepatoblastoma

肝母细胞瘤（Hepatoblastoma, HB）是儿童最主要的肝脏恶性肿瘤，针对侵袭性肿瘤患者的治疗选择极为有限，且该病属于罕见病。本研究对32例HB患者开展了高通量分子学研究，并在额外80例病例中验证了核心研究结果。研究揭示了一套表观遗传学特征谱，涵盖RNA编辑水平下调、肿瘤抑制基因BLCAP的超编辑、14q32染色体区域DLK1-DIO3基因座过表达、DNA低甲基化以及CpG岛高甲基化。基于上述发现，本研究确立了HB的整合性分子分型体系，该体系可优化当前的临床分层策略，并鉴定出CHKA可作为不良预后亚型的治疗靶点。实验设计概述：对32例HB患者的52份样本进行了组学特征分析。