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| Status |
Public on Apr 23, 2015 |
| Title |
Methylation data from presentation and relapsed medulloblastoma tumour samples |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
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| Summary |
We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of Trp53 function in this model produced aggressive tumors that mimicked the characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity, genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53–MYC interactions which emerge at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Using this dataset, assignation of medulloblastoma molecular subgroup by Illumina 450k microarray was performed for diagnostic and relapsed medulloblastoma samples to compare subgroup membership at diagnosis and relapse.
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| Overall design |
We investigated the DNA methylation profiles of 18 diagnostic and 22 relapsing samples (including 15 diagnostic / relapse pairs) using the Illumina 450k methylation microarray
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| Contributor(s) |
Schwalbe EC, Hill RM, Clifford SC |
| Citation(s) |
25533335 |
| Submission date |
Oct 22, 2014 |
| Last update date |
Mar 22, 2019 |
| Contact name |
Ed Schwalbe |
| E-mail(s) |
ed.schwalbe@northumbria.ac.uk
|
| Organization name |
Northumbria University
|
| Department |
Applied Sciences
|
| Street address |
Ellison Place
|
| City |
Newcastle upon Tyne |
| ZIP/Postal code |
NE1 8ST |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL13534 |
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482) |
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| Samples (40)
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| This SubSeries is part of SuperSeries: |
| GSE62626 |
Combined MYC and TP53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease |
|
| Relations |
| BioProject |
PRJNA266444 |
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