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Differential Expression of Genes for Ubiquitin Ligases in Medulloblastoma Subtypes

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Abstract

Using publically available datasets on gene expression in medulloblastoma (MB) subtypes, we selected genes for ubiquitin ligases and identified statistically those that best predicted each of the four major MB subgroups as separate disease entities. We identify a gene coding for an ubiquitin ligase, ZNRF3, whose overexpression alone can predict the WNT subgroup for 100% in the Pfister dataset. For the SHH subgroup, we identify a gene for a regulatory subunit of the protein phosphatase 2A (PP2A), PPP2R2C, as the major predictor among the E3 ligases genes. The ubiquitin and ubiquitin-like conjugation database (UUCD) lists PPP2R2C as coding for a Cullin Ring ubiquitin ligase adaptor. For group 3 MBs, the best ubiquitin ligase predictor was PPP2R2B, a gene which codes for another regulatory subunit of the PP2A holoenzyme. For group 4, the best E3 gene predictors were MID2, ZBTB18, and PPP2R2A, which codes for a third PP2A regulatory subunit. Heatmap analysis of the E3 gene data shows that expression of ten genes for ubiquitin ligases can be used to classify MBs into the four major consensus subgroups. This was illustrated by analysis of gene expression of ubiquitin ligases of the Pfister dataset and confirmed in the dataset of Cavalli. We conclude that genes for ubiquitin ligases can be used as genetic markers for MB subtypes and that the proteins coded for by these genes should be investigated as subtype specific therapeutic targets for MB.

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Authors and Affiliations

  1. Department of Human Anatomy & Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Rm134, BMSB, 745 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0J9, Canada

    Jerry Vriend

  2. Department of Community Health Sciences, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

    Robert B. Tate

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Table S1

Excel file of differentially expressed genes for ubiquitin ligases in the Pfister dataset (XLSX 31 kb)

Table S2

Excel file of other differentially expressed genes functionally related to ubiquitin ligases (XLSX 15 kb)

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Vriend, J., Tate, R.B. Differential Expression of Genes for Ubiquitin Ligases in Medulloblastoma Subtypes. Cerebellum 18, 469–488 (2019). https://doi.org/10.1007/s12311-019-1009-y

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