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Series GSE131473 Query DataSets for GSE131473
Status Public on Jun 27, 2020
Title Wnt activation as a therapeutic strategy in medulloblastoma
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Medulloblastoma (MB), the most common malignant pediatric brain tumor, is defined by four molecular subgroups (Wnt, Shh, Group 3, Group 4) based on transcriptional and epigenetic profiles. Wnt MB accounts for 10% of cases with the majority harboring somatic CTNNB1 mutations and chromosomal alterations for monosomy 6. Clinically, Wnt MBs have the most favorable prognosis with a >95% 5-year survivorship. By contrast, non-Wnt MBs are characterized by metastatic disease, increased rates of recurrence, and intermediate-poor overall survivorship. Given that Wnt MBs represent the only subgroup in which metastasis is not indicative of a poor prognosis, it has been suggested that Wnt signaling may contribute to their remarkable response to therapy. Using primary patient-derived MB brain tumor-initiating cell (BTIC) lines, we have characterized intrinsic differences in the tumor-initiating capacity of Wnt and non-Wnt MBs. In this work, we aimed to discover if Wnt activation in non-Wnt MBs could serve as a rationale for therapy employing a novel substrate-competitive peptide Wnt agonist. Our preclinical work establishes activated Wnt signaling as an innovative treatment paradigm with high clinical utility in childhood MB and provides evidence for the context-specific tumor suppressive function of the Wnt/β-catenin pathway.
Overall design We compared the transcriptome of MB BTIC lines generated from Wnt (BT853), Group 3 (SU_MB002), and Group 4 (ICB1299). Each sample had triplicates (A, B, C). Further, we compared the transcriptome of control (PBS) and Wnt-activating drug-treated (L807mts) samples for SU_MB002 and ICB1299. These were also prepared in triplicates (A, B, C). Lastly, we compared the transcriptome of SU_MB002 cells that were flow cytometrically sorted for expression of endogenous Wnt activity based on TCF reporter expression for GFP (TGP_POS) compared to those cells that were negative based on TCF reporter expression for GFP (TGP_NEG). These samples were also prepared and analyzed as triplicates (A, B, C).
Contributor(s) Manoranjan B, Venugopal C, Dvorkin-Gheva A, Singh SK
Citation(s) 32859895
Submission date May 20, 2019
Last update date Sep 08, 2020
Contact name Sheila Singh
Organization name McMaster University
Department Biochemistry and Biomedical Sciences
Street address 1280 Main Street West
City Hamilton
State/province ON
ZIP/Postal code L8S4K1
Country Canada
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (27)
GSM3781247 BT853_A
GSM3781248 BT853_B
GSM3781249 BT853_C
BioProject PRJNA543788
SRA SRP198924

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Supplementary file Size Download File type/resource
GSE131473_AllFiles_HISAT_USCS_VOOM_TMM.csv.gz 1.7 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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