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Epigenetic footprint of hepatoblastoma defines a novel integrative molecular classification with clinical implications

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE132219 | GEO | 2020/03/23

REPOSITORIES: GEO

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Epigenetic footprint of hepatoblastoma defines a novel integrative molecular classification with clinical implications [CytoScanHD_Array]

Project description: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.

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

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Epigenetic footprint of hepatoblastoma defines a novel integrative molecular classification with clinical implications

Project description:Epigenetic footprint of hepatoblastoma defines a novel integrative molecular classification with clinical implications

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Epigenetic footprint of hepatoblastoma defines a novel integrative molecular classification with clinical implications [CytoScanHD_Array]

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Epigenetic footprint of hepatoblastoma defines a novel integrative molecular classification with clinical implications [Infinium MethylationEPIC]

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Epigenetic footprint of hepatoblastoma defines a novel integrative molecular classification with clinical implications [RNA-seq]

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Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma.

Project description:Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel the genetic/epigenetic basis of RMS. On the basis of methylation patterns, RMS is clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes and clinical behaviours. A1 and A2 subtypes, especially A1, largely correspond to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes are characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite the better prognosis of embryonal RMS, patients in the E2 are likely to have a poor prognosis. Our results highlight the close relationships of the methylation status and gene mutations with the biological behaviour in RMS.

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