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Series GSE17224 Query DataSets for GSE17224
Status Public on Dec 05, 2009
Title DNA methylation of developmental genes in pediatric medulloblastomas identified by DAMD
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary DNA methylation might have a significant role in preventing normal differentiation in pediatric cancers. We used a genomewide method for detecting regions of CpG methylation on the basis of the increased melting temperature of methylated DNA, termed denaturation analysis of methylation differences (DAMD). Using the DAMD assay, we find common regions of cancer-specific methylation changes in primary medulloblastomas in critical developmental regulatory pathways, including Sonic hedgehog (Shh), Wingless (Wnt), retinoic acid receptor (RAR), and bone morphogenetic protein (BMP). One of the commonly methylated loci is the PTCH1-1C promoter, a negative regulator of the Shh pathway that is methylated in both primary patient samples and human medulloblastoma cell lines. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-dC) increases the expression of PTCH1 and other methylated loci. Whereas genetic mutations in PTCH1 have previously been shown to lead to medulloblastoma, our study indicates that epigenetic silencing of PTCH1, and other critical developmental loci, by DNA methylation is a fundamental process of pediatric medulloblastoma formation. This finding warrants strong consideration for DNA demethylating agents in future clinical trials for children with this disease.
Overall design Genome-wide DNA methylation profiles generated using the Denaturation Analysis of Methylation Differences (DAMD) assay. Samples analyzed: Colo320DM vs. HDF; HCT116 vs. DKO; and 4 primary human medulloblastoma samples vs. adult normal cerebellum
Contributor(s) Diede SJ, Guenthoer J, Geng LN, Mahoney SE, Marotta M, Olson JM, Tanaka H, Tapscott SJ
Citation(s) 19966297
Submission date Jul 21, 2009
Last update date Mar 21, 2017
Contact name Scott J. Diede
Organization name Fred Hutchinson Cancer Research Center
Street address 1100 Fairview Avenue North, Mailstop c3-168
City Seattle
State/province WA
ZIP/Postal code 98109
Country USA
Platforms (3)
GPL4910 [Hs35b_P01R] Affymetrix Human Tiling 2.0R Set, Array 1
GPL4913 [Hs35b_P04R] Affymetrix Human Tiling 2.0R Set, Array 4
GPL5082 [Hs_PromPR] Affymetrix Human Promoter 1.0R Array
Samples (15)
GSM431429 Colo320DMvHDFA_DAMD
GSM431430 Colo320DMvHDFA_50form
GSM431431 Colo320DMvHDFD_DAMD
BioProject PRJNA119191

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE17224_RAW.tar 1.6 Gb (http)(custom) TAR (of BAR, CEL)
Processed data provided as supplementary file

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