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| 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
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| 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.
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| 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
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| Contributor(s) |
Diede SJ, Guenthoer J, Geng LN, Mahoney SE, Marotta M, Olson JM, Tanaka H, Tapscott SJ |
| Citation(s) |
19966297 |
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| Submission date |
Jul 21, 2009 |
| Last update date |
Mar 21, 2017 |
| Contact name |
Scott J. Diede |
| E-mail(s) |
scott.diede@merck.com
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| Organization name |
Fred Hutchinson Cancer Research Center
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| Street address |
1100 Fairview Avenue North, Mailstop c3-168
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
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| 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 |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA119191 |
| 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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