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Series GSE130178 Query DataSets for GSE130178
Status Public on Oct 09, 2019
Title β-Catenin mutations as determinants of hepatoblastoma phenotypes in mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Hepatoblastoma (HB) is the most common pediatric liver cancer. While long-term survival is generally favorable, it is dependent upon clinical stage, tumor histology and a variety of biochemical and molecular features. HB appears almost exclusively before the age of three years, is represented by seven histologic subtypes and is usually associated with highly heterogeneous somatic mutations in the CTNNB1 gene, which encodes b-catenin, a Wnt ligand-responsive transcriptional co-factor. Numerous recurrent b-catenin mutations, not previously documented in HB, have also been identified in various other pediatric and adult cancer types. Little is known regarding the underlying factors that determine the above HB features and behaviors or whether non-HB-associated b-catenin mutations are tumorigenic when expressed in hepatocytes. Here, we investigated the oncogenic properties of 14 different HB- and non-HB-associated b-catenin mutants encoded by Sleeping Beauty vectors following their delivery into the liver by hydrodynamic tail vein injection. We show that all b-catenin mutations, as well as wild-type b-catenin are tumorigenic when co-expressed with a mutant form of yes-associated protein. However, tumor growth rates, histologies, nuclear:cytoplasmic partitioning and metabolic and transcriptional landscapes were strongly influenced by the identities of the b-catenin mutations. These findings provide a context for understanding at the molecular level the notable biological diversity of this important pediatric cancer.
Overall design RNA purification from five representative tumors of each group was performed using Qiagen RNAeasy columns (Qiagen, Inc., Valencia, CA) followed by DNase digestion. Sample integrity was measured using an Agilent 2100 Bioanalyzer (Agilent Technologies, Foster City, CA). All samples had RIN values of 8.5-10 prior to any further processing. Samples for sequencing were prepared using an NEB NEBNext Ultra Directional RNA Library Prep kit according to the directions provided by the vendor (New England Biolab, Beverly, MA) and sequencing was performed on a NovaSeq 6000 Instrument (Illumina, Inc., San Diego, CA) by Novagene, Inc. (Sacramento, CA).
Contributor(s) Wang H, Prochownik EV
Citation(s) 31597698, 35259493
Submission date Apr 23, 2019
Last update date Aug 28, 2023
Contact name Edward V Prochownik
Phone 412-692-6795
Organization name Children’s Hospital of Pittsburgh of UPMC
Department Division of Hematology/Oncology
Street address 4401 Penn Ave.
City Pittsburgh
State/province PA
ZIP/Postal code 15224
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (50)
GSM3733397 Tumor_Del20-32_s1766
GSM3733398 Tumor_Del20-32_s1769
GSM3733399 Tumor_Del20-32_s1780
BioProject PRJNA534224
SRA SRP193449

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Supplementary file Size Download File type/resource
GSE130178_Expression_Browser_-CLC.xlsx 89.9 Mb (ftp)(http) XLSX
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Processed data are available on Series record

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