Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

New insights into diagnosis and therapeutic options for proliferative hepatoblastoma

ABSTRACT: New insights into diagnosis and therapeutic options for proliferative hepatoblastoma

PROVIDER: PRJNA413799 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR6154700_1.fastq.gz	Fastqsanger.gz
	SRR6154700_2.fastq.gz	Fastqsanger.gz
	SRR6154710_1.fastq.gz	Fastqsanger.gz
	SRR6154710_2.fastq.gz	Fastqsanger.gz
	SRR6154720_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 124

Similar Datasets

New insights into diagnosis and therapeutic options for proliferative hepatoblastoma

Project description:Surgery and cisplatin-based treatment of hepatoblastoma (HB) currently guarantee the survival of 70-80% of patients. However, some important challenges remain in diagnosing high risk tumors and identifying relevant targetable pathways offering new therapeutic avenues. Previously, two molecular subclasses of hepatoblastoma tumors have been described, namely C1 and C2; C2 being the subgroup with the poorest prognosis, a more advanced tumor stage and the worst overall survival rate. An associated 16-gene signature to discriminate the two tumoral subgroups was proposed but it has not been transferred into clinical routine. To address these issues we performed RNA sequencing of 25 tumors and matched normal liver samples from patients. The transcript profiling separated HB into three distinct subgroups named C1, C2A and C2B, identifiable by a concise four-gene signature: HSD17B6, ITGA6, TOP2A and VIM, with TOP2A being characteristic for the proliferative C2A tumors. Differential expression of these genes was confirmed by RT-qPCR on an expanded cohort and by immunohistochemistry. We also revealed significant overexpression of genes involved in Fanconi Anemia (FA) pathway in the C2A subgroup. We then investigated the ability of several described FA inhibitors to block growth of HB cells in vitro and in vivo. We demonstrated that bortezomib, an FDA-approved proteasome inhibitor, strongly impairs the proliferation and survival of HB cell lines in vitro, blocks FA pathway associated double-strand DNA repair and significantly impedes HB growth in vivo. In conclusion, the highly proliferating C2A subtype is characterized by TOP2A gene up-regulation and FA pathway activation and HB therapeutic arsenal could include Bortezomib for the treatment of patients with the most aggressive tumors.

2017-11-21 | GSE104766 | GEO

Modeling Hepatoblastoma

Project description:Modeling Hepatoblastoma

| PRJNA749045 | ENA

Hepatic transcriptome of pediatric hepatoblastoma.

Project description:The mechanisms underlying hepatoblastoma are not well defined. To address this, we generated transcriptomic profiles of normal, background, and hepatoblastoma liver samples from patients aged 0.01 months to 6 years, using RNA-sequencing. Hepatoblasoma was histologically confirmed. Here we focus on the elevation of stem cell markers and the loss of tumor suppressor proteins leading to the development of hepatoblastoma in very young children.

2018-07-01 | GSE81928 | GEO

Genome-wide mapping of ASCL2 and CTNNB1 in hepatoblastoma cell lines

Project description:Hepatoblastoma (HB) is the most common pediatric liver malignancy; however, hereditary predisposition and acquired molecular aberrations related to HB clinicopathological diversity are not well understood. We performed an integrative genomic profiling of 163 pediatric liver tumors (154 HB and 9 hepatocellular carcinoma) based on data acquired from a cohort study (JPLT-2). The total number of somatic mutations was found to be extremely low (0.52 /Mb on exonic regions) but correlated with age at diagnosis. TERT promoter mutations are prevalent in the tween HBs, selective in the transitional liver cell tumor (TLCT, > 8 years old). DNA methylation profiling revealed that classical HBs are characterized by the specific hypomethylated enhancers, which are enriched with binding sites for ASCL2, a regulatory transcription factor for definitive endoderm in Wnt-pathway. Prolonged upregulation of ASCL2, as well as fetal-liver-like methylation patterns of IGF2 promoters, suggests their “cell of origin” derived from the premature hepatoblast, similar to intestinal epithelial cells, which are highly proliferative. Systematic molecular profiling of HB is a promising approach to understanding the epigenetic drivers of hepatoblast carcinogenesis and clues for risk stratification.

2021-06-01 | GSE169566 | GEO

hepatoblastoma WES

Project description:WES sequencing of 34 hepatoblastoma tumors and controls

| PRJEB11805 | ENA

Volasertib preclinical activity in high-risk hepatoblastoma

Project description:Relapsed and metastatic hepatoblastoma represents an unmet clinical need with limited chemotherapy treatment options. In a chemical screen, we identified volasertib as an agent with in vitro activity, inhibiting hepatoblastoma cell growth while sparing normal hepatocytes. Volasertib targets PLK1 and prevents the progression of mitosis, resulting in eventual cell death. PLK1 is overexpressed in hepatoblastoma biopsies relative to normal liver tissue. As a potential therapeutic strategy, we tested the combination of volasertib and the relapse-related hepatoblastoma chemotherapeutic irinotecan. We found both in vitro and in vivo efficacy of this combination, which may merit further preclinical investigation and exploration for a clinical trial concept.

| EGAS00001004827 | EGA

Genome-wide analysis of long noncoding RNA (lncRNA) expression in hepatoblastoma tissues

2013-12-31 | GSE51701 | GEO

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.

2020-03-23 | GSE132218 | GEO

Targeting the unwindosome by mebendazole is a vulnerability of chemoresistant hepatoblastoma

Project description:We identified mebendazole as a drug to circumvent chemoresistance in hepatoblastoma cell lines that are resistant to cisplatin. In order to identify the mechanistic basis of mebendazole function, we performed gene expression analysis of three mebendazole-treated hepatoblastoma cell lines.

2022-07-28 | GSE209824 | GEO

Genome-wide analysis of long noncoding RNA (lncRNA) expression in hepatoblastoma tissues

Project description:We performed a genome-wide analysis of lncRNA expression in hepatoblastoma tissues to identify novel targets for further study of hepatoblastoma.We found that 2736 lncRNAs were differentially expressed in hepatoblastoma tissues. The genome-wide analysis of lncRNA expression in these tissues was performed using a 4 M-CM-^W 180K lncRNA microarray and Sureprint G3 Human lncRNA Chips.Quantitative RT-PCR (qRT-PCR) was performed to confirm these results.

2013-12-31 | E-GEOD-51701 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data