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Updated: Jun 1, 2026
Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
Published on: September 1, 2010
PCDH10 is a candidate tumour suppressor gene in medulloblastoma
Kelsey C Bertrand1, Stephen C Mack, Paul A Northcott
1Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumor Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, M4N 1X8, Canada.
Purpose:
The aim of this study was to investigate the genetic and epigenetic mechanisms contributing to PCDH10 down-regulation in medulloblastoma. We examined the role of PCDH10 as a mediator of medulloblastoma cell proliferation, cell cycle progression, and cell migration.
Methods:
We identified a focal homozygous deletion of PCDH10 in medulloblastoma by surveying a cohort of 212 tumours by Affymetrix SNP array analysis. PCDH10 expression was assessed by quantitative reverse transcriptase PCR in a series of 26 tumours. The promoter methylation status of PCDH10 was determined using methylation specific PCR and Sequenom MassCLEAVE analysis. Functional studies examining the role of PCDH10 in medulloblastoma development were performed by re-expression of PCDH10 in the DAOY medulloblastoma cell line, and then, cell proliferation, cell cycle distribution, and cell migration assays were performed.
Results:
We report a very focal homozygous deletion on chromosome 4q28.3 harbouring the PCDH10 gene. We demonstrate that PCDH10 transcription is down-regulated in 19/26 (73%) of medulloblastomas suggesting that other mechanisms also could be involved in gene repression. We found that DNA hypermethylation contributed to the deregulation of PCDH10 in 11/44 (25%) of medulloblastoma cell lines and primary tumours. Using a stable cell line (DAOY) re-expressing PCDH10, we observed that cell migration was impaired upon restoration of PCDH10 expression.
Conclusions:
Our findings suggest that genetic and epigenetic deregulation of PCDH10 occurs in a significant portion of medulloblastoma patients. Failure to express PCDH10 may result in loss of inhibition of cell migration, thereby contributing to medulloblastoma progression.
Insights
Genetic and epigenetic changes down-regulate PCDH10 in medulloblastoma. Loss of PCDH10 expression impairs cell migration inhibition, potentially driving tumor progression.
Area of Science:
- Oncology
- Genetics
- Epigenetics
Background:
- Medulloblastoma is a common pediatric brain tumor with complex genetic underpinnings.
- Altered gene expression, including down-regulation of tumor suppressors, is a hallmark of medulloblastoma.
- The role of Protocadherin 10 (PCDH10) in medulloblastoma pathogenesis remains largely unexplored.
Purpose of the Study:
- To investigate genetic and epigenetic mechanisms causing PCDH10 down-regulation in medulloblastoma.
- To assess PCDH10's role in medulloblastoma cell proliferation, cell cycle, and migration.
Main Methods:
- Surveyed 212 medulloblastoma tumors for PCDH10 deletions using Affymetrix SNP array.
- Quantified PCDH10 expression via RT-PCR in 26 tumors.
- Analyzed PCDH10 promoter methylation using methylation-specific PCR and Sequenom MassCLEAVE.
- Performed functional assays in PCDH10-re-expressing DAOY medulloblastoma cells.
Main Results:
- Identified a focal homozygous deletion of PCDH10 in chromosome 4q28.3.
- Observed PCDH10 down-regulation in 73% of medulloblastomas.
- Found DNA hypermethylation contributing to PCDH10 deregulation in 25% of samples.
- Restoration of PCDH10 expression impaired cell migration in DAOY cells.
Conclusions:
- Genetic and epigenetic alterations of PCDH10 are prevalent in medulloblastoma.
- Loss of PCDH10 expression may disinhibit cell migration, promoting medulloblastoma progression.
- PCDH10 represents a potential therapeutic target in medulloblastoma.
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