title: PCDH10 is a candidate tumour suppressor gene in medulloblastoma.
abstract: OBJECTIVE
  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.
authors: Division 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.
authors: Kelsey C
authors: KC
authors: Bertrand
authors: Stephen C
authors: SC
authors: Mack
authors: Paul A
authors: PA
authors: Northcott
authors: Livia
authors: L
authors: Garzia
authors: Adrian
authors: A
authors: Dubuc
authors: Stefan M
authors: SM
authors: Pfister
authors: James T
authors: JT
authors: Rutka
authors: William A
authors: WA
authors: Weiss
authors: Michael D
authors: MD
authors: Taylor
references: Neuro Oncol. 2007 Oct;9(4):460-4
references: 17704358
references: Am J Obstet Gynecol. 2011 Jan;204(1):21.e1-7
references: 20833385
references: Neurosurg Focus. 2010 Jan;28(1):E6
references: 20043721
references: J Clin Oncol. 2011 Apr 10;29(11):1408-14
references: 20823417
references: J Clin Oncol. 2010 Mar 10;28(8):1345-50
references: 20142599
references: J Clin Oncol. 2006 Apr 20;24(12):1924-31
references: 16567768
references: Oncogene. 2004 Jun 3;23(26):4577-83
references: 15077159
references: Nat Genet. 2009 Apr;41(4):465-72
references: 19270706
references: Neoplasma. 2010;57(3):247-52
references: 20353276
references: Am J Med Genet A. 2005 May 1;134(4):399-403
references: 15759260
references: Cancer Res. 2009 Apr 15;69(8):3249-55
references: 19351822
references: Clin Neurosurg. 2000;47:259-302
references: 11197707
references: Neuro Oncol. 2010 Dec;12(12):1311-7
references: 20713408
references: Clin Cancer Res. 2009 Jun 1;15(11):3881-8
references: 19470736
references: Childs Nerv Syst. 2006 Nov;22(11):1379-94
references: 16951964
references: Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):20007-12
references: 18077431
references: Nat Genet. 2002 Jul;31(3):306-10
references: 12068298
references: Cancer Invest. 1998;16(4):252-61
references: 9589034
references: Int J Cancer. 2005 Sep 1;116(3):407-14
references: 15818620
references: Cancer. 2007 Mar 1;109(5):899-906
references: 17236224
references: Blood. 2008 Feb 15;111(4):2382-4
references: 18055864
references: Childs Nerv Syst. 2000 Nov;16(10-11):809-20
references: 11151735
references: Neuro Oncol. 2006 Jul;8(3):244-52
references: 16723629
references: J Clin Oncol. 2004 Mar 15;22(6):984-93
references: 14970185
references: Eur J Paediatr Neurol. 2003;7(2):53-66
references: 12697428
references: Pediatr Neurosurg. 2001 Nov;35(5):235-8
references: 11741116
references: Neurosurgery. 2000 Oct;47(4):888-901
references: 11014429
references: Genes Chromosomes Cancer. 2009 Nov;48(11):983-92
references: 19681120
references: Bioessays. 1999 Dec;21(12):1021-30
references: 10580987
references: J Clin Oncol. 2011 Apr 10;29(11):1424-30
references: 21098324
references: Curr Oncol. 2009 Dec;16(6):21-8
references: 20016743
references: Oncogene. 2006 Feb 16;25(7):1070-80
references: 16247458