CTNNB1 is the most frequently mutated gene in hepatocellular carcinoma (HCC). However, its clinical relevance remains controversial. We determined an evolutionarily conserved -catenin signature by comparative analysis of gene expression data from human HCC and a mouse model (GSE43628). We generated gene expression data from the tumors of 88 HCC patients who underwent surgical resection as the primary treatment. We used these gene expression data to develop a new prognostification model for prognosis of HCC after surgery.
Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesExpression profiling of hepatocytes-derived ductal cells with properties intermediate between mature hepatocytes and cholangiocytes Overall design: Chimeric adult mice were generated where mature hepatocytes were marked with a fluorescent red marker. Chronic injury was induced for ~6weeks and three cell types were isolated by FACS (Influx, BD) for expression analysis by RNAseq based on cell surface phenotype and origin: hepatocytes (n=3), hepatocyte-derived oval cells (1c3+, n=5), and cholangiocyte-derived oval cells (1c3+, n=5).
Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes.
No sample metadata fields
View SamplesCTNNB1 is the most frequently mutated gene in hepatocellular carcinoma (HCC). However, its clinical relevance remains controversial. We determined an evolutionarily conserved -catenin signature by comparative analysis of gene expression data from human HCC (GSE43619) and a mouse model.
Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis.
Specimen part
View SamplesFumarylacetoacetate hydrolase (Fah), the last enzyme of the tyrosine degradation pathway, is specifically expressed in hepatocytes in the liver. Loss of Fah leads to liver failure in mice within 6-8 weeks. This can be prevented by blocking tyrosine degradation upstream of Fah with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC). Here, we investigate the impact of p21 on global gene expression in Fah deficiency.
Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis.
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View SamplesAlthough expansion of a polyglutamine tract in ATAXIN1 (ATXN1) causes Spinocerebellar ataxia type 1, the functions of wild-type ATXN1 and ATAXIN1-Like (ATXN1L) remain poorly understood. To gain insight into the function of these proteins, we generated and characterized Atxn1L-/- and Atxn1-/- ; Atxn1L-/- double mutant animals. We found that Atxn1L -/- mice have several developmental problems including hydrocephalus, omphalocoele and lung alveolarization defects. These phenotypes are more penetrant and severe in Atxn1-/- ; Atxn1L-/- mice, suggesting that Atxn1 and Atxn1L are functionally redundant.
ATXN1 protein family and CIC regulate extracellular matrix remodeling and lung alveolarization.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups.
Sex, Age, Specimen part, Race
View SamplesHepatoblastoma (HB) is the most common liver cancer in children, but few pre-treatment tumors have been molecularly profiled. Consequently, there are no validated prognostic or therapeutic biomarkers for HB patients. We report on molecular analysis of 88 clinically-annotated HB tumors. This analysis pointed to three risk-stratifying molecular subtypeslow, intermediate and high riskthat are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways. High-risk tumors are characterized by high NFE2L2 activity and LIN28B, HMGA2, SALL4 and AFP expression, low let-7 expression and HNF1A activity, and high coordinated expression of oncofetal proteins and stem cell markers. Tests on a 35 HB validation set supported these genes as prognostic biomarkers.
Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups.
Sex, Specimen part, Race
View SamplesGene expression profiling was carried out in six (wild type, ß2SP+/-, ß2SP-/-, SMAD3+/-, SMAD3-/- and ß2SP+/-/ SMAD3+/-) different mouse knockout embryonic fibroblast (MEF) cells. Beta-2-spectrin (ß2SP) is a dynamic intracellular non-pleckstrin homology (PH)-domain protein that belongs to a family of polypeptides that have been implicated in conferring cell polarity. Spectrins have been linked to multiple signaling pathways, including cell cycle regulation, DNA repair and TGFß signaling. In this study, we report a major role of the TGFß/Smad3 adaptor ß2-Spectrin in conserving genomic integrity from alcohol-induced DNA damage and describe a novel pathway that protects genomes from genotoxic stresses. To determine the mechanism for the oncogenic switch, and whether it is related to the role of ß2SP in TGF-ß signaling transduction or secondary to its cytoskeletal functions, we analyzed disruption of two elements of the TGF-ß pathway by generating double heterozygous Sptbn1+/-/Smad3+/- mice. Overall design: Whole-transcriptome RNA sequencing MEF cells of the following genotypes was carried out on an Illumina HiSeq 2000 sequencer: wildtype, heterozygous Beta-2-spectrin knockout (ß2SP+/-), homozygous Beta-2-spectrin knockout (ß2SP-/-), heterozygous SMAD3 (Mothers against decapentaplegic, Drosophila, Homolog of 3, SMAD3+/-), homozygous knockout SMAD3-/-, and double heterozygous mutation of Beta-2-spectrin and SMAD3 (ß2SP+/-/ SMAD3+/-).
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.
No sample metadata fields
View SamplesGene expression profiling was carried out in two liver tumors and one normal liver isolated from ß2SP+/-; SMAD3+/- mice, and one normal liver isolated from wild type mouse. Whole-transcriptome sequencing of these 4 liver tissues. Overall design: Whole-transcriptome RNA sequencing of the 4 different samples
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.
No sample metadata fields
View SamplesGene expression profiling was carried out in one normal human fibroblast cell line established from normal people and three different cell lines established from BWS patients to characterize the molecular mechanisms relevant to the etiology of BWS and tumor development. Whole-transcriptome sequencing of three BWS fibroblastic cell lines was established from patients with mutation in the CDKN1C mutation (CDKN1C+ cell line), and loss of methylation in the KCNQ1OT1 region (KvDMR+ cell line: with KvDMR molecular defect, and KvDMR- cell line: absence of KvDMR molecular defect but it had some clinical signs of BWS) Overall design: Whole-transcriptome RNA sequencing of the 4 different cell lines
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.
No sample metadata fields
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