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http://purl.uniprot.org/citations/21597995http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21597995http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
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http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/author"Weiss W.A."xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/author"Northcott P.A."xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/author"Pfister S.M."xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/author"Taylor M.D."xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/author"Garzia L."xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/author"Rutka J.T."xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/author"Bertrand K.C."xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/author"Dubuc A."xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/name"Childs Nerv Syst"xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/pages"1243-1249"xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/title"PCDH10 is a candidate tumour suppressor gene in medulloblastoma."xsd:string
http://purl.uniprot.org/citations/21597995http://purl.uniprot.org/core/volume"27"xsd:string
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