Study of pediatric hepatocellular carcinoma with BSEP deficiency
Ontology highlight
ABSTRACT:
PROVIDER: EGAC00001000191 | EGA |
REPOSITORIES: EGA
Publications
Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency.
Iannelli Fabio F Collino Agnese A Sinha Shruti S Radaelli Enrico E Nicoli Paola P D'Antiga Lorenzo L Sonzogni Aurelio A Faivre Jamila J Buendia Marie Annick MA Sturm Ekkehard E Thompson Richard J RJ Knisely A S AS Natoli Gioacchino G Ghisletti Serena S Ciccarelli Francesca D FD
Nature communications 20140513
Hepatocellular carcinoma (HCC) is almost invariably associated with an underlying inflammatory state, whose direct contribution to the acquisition of critical genomic changes is unclear. Here we map acquired genomic alterations in human and mouse HCCs induced by defects in hepatocyte biliary transporters, which expose hepatocytes to bile salts and cause chronic inflammation that develops into cancer. In both human and mouse cancer genomes, we find few somatic point mutations with no impairment o ...[more]
Similar Datasets
Project description:Data Access Committee EGAC00001000628
| EGAC00001000628 | EGA
Project description:Data Access Committee EGAC00001000070
| EGAC00001000070 | EGA
Project description:Data Access Committee EGAC00001000627
| EGAC00001000627 | EGA
Project description:Development of a new carcinoma cell line (HC-AFW1) derived from a pediatric liver tumor The cell line HC-AFW1 was derived from a 4 year old boy suffering from HCC through culturing and passage into immuno-deficient mice. The cell line is stable now for over 8 months of culture with a doubling time of 40 h. The tumor cells show an epithelial histology and express hepatoma proteins such as Alpha-fetoprotein (AFP), Glypican 3, E-cadherin, CD10, CD326, HepPar1, Vimentin and Desmin. Catenin beta shows a deletion of 49 amino acids in the exon 3 involving the phosphorylation sites of GSK3 and is detectable in the cell nuclei. Cytogenetic analysis revealed large anomalies in the chromosomal map including chromosomal aberrations found in hepatoblastoma as well as in adult HCC.
2011-12-01 | GSE29283 | GEO
Project description:Development of a new carcinoma cell line (HC-AFW1) derived from a pediatric liver tumor The cell line HC-AFW1 was derived from a 4 year old boy suffering from HCC through culturing and passage into immuno-deficient mice. The cell line is stable now for over 8 months of culture with a doubling time of 40 h. The tumor cells show an epithelial histology and express hepatoma proteins such as Alpha-fetoprotein (AFP), Glypican 3, E-cadherin, CD10, CD326, HepPar1, Vimentin and Desmin. Catenin beta shows a deletion of 49 amino acids in the exon 3 involving the phosphorylation sites of GSK3 and is detectable in the cell nuclei. Cytogenetic analysis revealed large anomalies in the chromosomal map including chromosomal aberrations found in hepatoblastoma as well as in adult HCC. Copy number analysis of two different passages of HC-AFW1 cells Two tumor specimens were used for tissue culture and xenotransplantation into NSG mice. Tumor cells derived from xenografts were cultured and designated as HC-AFW1. DNA was analyzed from the passage 2 (2P2). HC-AFW2 was derived from tissue culture without transfer in to mice. Primary tissue samples were minced into pieces of 3x3 mm and cultured on 6 well plates (Becton Dickenson, Frankfurt, Germany) in DMEM (GIBCO BRL, Carlsbad, CA) supplemented with 10% FCS (growth medium). Cell cultures were maintained in a humidified atmosphere containing 5% CO2 at 37°C. For subculturing cells were detached from the culture surface using accutase in Dulbecco´s PBS containing 0.5mM EDTA (PAA Laboratories GmbH, Cölbe, Germany) for 2-3 minutes at 37°C. A sub-cultivation ratio of 1:4 and 1:6 was performed twice per week. Cells were stored in liquid nitrogen as a suspension in complete growth medium with 10% DMSO. DNA from patient blood and tumor samples was isolated with the QiaAmp DNA mini Kit according to manufacturer's instructions (Qiagen, Hilden, Germany). Single nucleotide polymorphism (SNP) and copy number polymorphism (CNP) genotyping were performed using the Genome-Wide Human SNP Array 6.0 and Genotyping Console (GTC) software (Affymetrix, Santa Clara, CA).
2011-12-01 | E-GEOD-29283 | biostudies-arrayexpress
Project description:Genetically modified mice have been extensively used for analyzing the molecular events that occur during the tumor development. However, in many cases, if not all, it is uncertain to what extent the mouse models reproduce features observed in the corresponding human conditions. This is due largely to lack of precise methods for direct and comprehensive comparison at the molecular level of the mouse and human tumors. We used global gene expression patterns of 68 hepatocellular carcinoma (HCC) from 7 different mouse models and 91 human HCC from pre-defined subclasses to obtain direct comparison of the molecular features of mouse and human HCC. Total RNAs were isolated from frozen liver tissue using CsCl density gradient centrifugation methods. Total RNA from the livers of 10 wild type mice were pooled and used as reference in entire microarray experiments. To obtain gene expression profile data from four transgenic HCC mouse models, 20 μg of total RNAs from tissues were used to drive fluorescently (Cy-5 or Cy-3) labeled cDNA. At least two hybridizations were carried out for each tissue using dye-swap strategy to eliminate dye labeling bias. Keywords: other
2004-10-28 | GSE1897 | GEO
Project description:Global gene expression patterns of 91 human hepatocellular carcinomas (HCC) were analyzed to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Total RNAs were isolated from frozen liver tissue using CsCl density gradient centrifugation methods. Total RNA from 18 normal livers were pooled and used as reference in entire microarray experiments. To obtain gene expression profile data from human HCC, 20 μg of total RNAs from tissues were used to drive fluorescently (Cy-5 or Cy-3) labeled cDNA. At least two hybridizations were carried out for each tissue using dye-swap strategy to eliminate dye labeling bias. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with survival of the patients. This association was validated by five independent supervised learning methods. Genes most strongly associated with survival were identified by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provides new molecular insight into the pathogenesis of HCC. Tumors from the low survival subclass have strong cell proliferation and anti-apoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and histone modification suggesting an etiological involvement of these processes in accelerating the progression of HCC. The biological differences identified in the HCC subclasses should provide an attractive source for the development of therapeutic targets (e.g. HIF1a) for selective treatment(s) of HCC patients. Keywords: other
2004-10-28 | GSE1898 | GEO
Project description:Genetically modified mice have been extensively used for analyzing the molecular events that occur during the tumor development. However, in many cases, if not all, it is uncertain to what extent the mouse models reproduce features observed in the corresponding human conditions. This is due largely to lack of precise methods for direct and comprehensive comparison at the molecular level of the mouse and human tumors. We used global gene expression patterns of 68 hepatocellular carcinoma (HCC) from 7 different mouse models and 91 human HCC from pre-defined subclasses to obtain direct comparison of the molecular features of mouse and human HCC. Total RNAs were isolated from frozen liver tissue using CsCl density gradient centrifugation methods. Total RNA from the livers of 10 wild type mice were pooled and used as reference in entire microarray experiments. To obtain gene expression profile data from four transgenic HCC mouse models, 20 μg of total RNAs from tissues were used to drive fluorescently (Cy-5 or Cy-3) labeled cDNA. At least two hybridizations were carried out for each tissue using dye-swap strategy to eliminate dye labeling bias.
2004-10-28 | E-GEOD-1897 | biostudies-arrayexpress
Project description:Global gene expression patterns of 91 human hepatocellular carcinomas (HCC) were analyzed to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Total RNAs were isolated from frozen liver tissue using CsCl density gradient centrifugation methods. Total RNA from 18 normal livers were pooled and used as reference in entire microarray experiments. To obtain gene expression profile data from human HCC, 20 μg of total RNAs from tissues were used to drive fluorescently (Cy-5 or Cy-3) labeled cDNA. At least two hybridizations were carried out for each tissue using dye-swap strategy to eliminate dye labeling bias. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with survival of the patients. This association was validated by five independent supervised learning methods. Genes most strongly associated with survival were identified by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provides new molecular insight into the pathogenesis of HCC. Tumors from the low survival subclass have strong cell proliferation and anti-apoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and histone modification suggesting an etiological involvement of these processes in accelerating the progression of HCC. The biological differences identified in the HCC subclasses should provide an attractive source for the development of therapeutic targets (e.g. HIF1a) for selective treatment(s) of HCC patients.
2004-10-28 | E-GEOD-1898 | biostudies-arrayexpress
Project description:Gene expression data from 100 human hepatocellular carcinomas (HCC) were generated and analyzed as part of effort for validating prognostic gene expression signatures from previous studies. Using four different classification algorithms and leave-one-out cross-validation approaches, four different prognostic signatures were applied to test the robustness and concordance of predicted outcome in individual patients. All four tumor-derived signatures were significantly associated with prognosis and had a high rate of concordance with predicted outcomes for individual patients. Total RNA was extracted from the fresh frozen tissues of 100 HCC. Five-hundred nanograms of total RNA were used for labeling and hybridization, according to the manufacturerâs protocols (Illumina). After the bead chips were scanned with an Illumina BeadArray Reader (Illumina), the microarray data were normalized using the quantile normalization method in the Linear Models for Microarray Data package in the R language environment. The expression level of each gene was transformed into a log 2 base before further analysis.
2010-07-08 | E-GEOD-16757 | biostudies-arrayexpress