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| Status |
Public on Jul 01, 2011 |
| Title |
Human medulloblastoma samples |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Purpose
Integrated genomics approaches have identified at least four distinct biological variants in medulloblastoma: WNT, SHH, group C, and group D. Non-WNT/Non-SHH tumors are associated with metastatic dissemination and an unfavorable prognosis. Additional markers may enhance outcome prediction in Non-WNT/Non-SHH medulloblastomas.
Experimental Design
We combined transcriptomic and DNA copy-number analyses for 64 primary medulloblastomas. Bioinformatic tools were applied to discover marker genes of molecular variants. Differentially expressed transcripts were evaluated for prognostic value in the screening cohort. Immunopositivity for FSTL5 was correlated with molecular and prognostic subgroups for 235 non-overlapping medulloblastoma samples on two independent tissue microarrays (TMA).
Results
Unsupervised clustering analyses of transcriptome profiles confirmed four distinct molecular variants. Stable subgroup separation was achieved using only the 300 most varying transcripts. Specific distributions of clinical and molecular characteristics were noted for each cluster. Distinct expression patterns of FSTL5 in each molecular subgroup were confirmed by quantitative real-time PCR. Immunopositivity of FSTL5 identified a large cohort of patients (84 of 235 patients; 36%) at high risk for relapse and death. Importantly, over 50% of Non-WNT/Non-SHH tumors displayed FSTL5 negativity, delineating a large patient cohort with an excellent prognosis who would be considered intermediate/high-risk based on current molecular subtyping.
Conclusions
Comprehensive analyses of transcriptomic and genetic alterations delineate four distinct variants of medulloblastoma. The addition of FSTL5 immunohistochemistry to existing molecular stratification schemes can effectively identify those Non-WNT/Non-SHH tumors with a poor outcome. Immunohistochemical staining for FSTL5 could be a high-quality and practical tool for stratification and prognostication in future clinical trials of medulloblastoma.
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| Overall design |
Whole-genome transcriptional profiling of human medulloblastomas. Subgrouping based on mRNA expression profiles.
Fresh frozen tumor material was collected during tumor resection. Dye-swap design used for expression profiling. Reference was a pool of normal cerebellum tissue from 24 donors. Gene expression profiles illustrate distinct expression pattern at diagnosis.
This submission represents the gene expression component of the study.
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| Contributor(s) |
Remke M, Hielscher T, Korshunov A, Northcott PA, Bender S, Kool M, Westermann F, Benner A, Cin H, Ryzhova M, Sturm D, Witt H, Haag D, Toedt G, Wittmann A, Schöttler A, von Bueren AO, Rutkowski S, Scheurlen W, Kulozik AE, Taylor MD, Lichter P, Pfister SM |
| Citation(s) |
21911727 |
| Submission date |
Mar 29, 2011 |
| Last update date |
Jan 23, 2019 |
| Contact name |
Marc Remke |
| E-mail(s) |
marcremke@gmail.com
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| Organization name |
The Hospital for Sick Children
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| Department |
Laboratory Medicine and Pathobiology
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| Street address |
555 University Ave. Rm 1504
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| City |
Toronto |
| ZIP/Postal code |
M5G 1X8 |
| Country |
Canada |
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| Platforms (1) |
| GPL6480 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version) |
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| Samples (64)
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| Relations |
| BioProject |
PRJNA139595 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE28245_RAW.tar |
1.7 Gb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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