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| Status |
Public on May 03, 2022 |
| Title |
Integrative Genomic Analysis of Medulloblastoma Identiļ¬es a Molecular Subgroup That Drives Poor Clinical Outcome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Medulloblastomas are heterogeneous tumors that collectively represent the most common malignant brain tumor in children. To understand the molecular characteristics underlying their heterogeneity and to identify whether such characteristics represent risk factors for patients with this disease, we performed an integrated genomic analysis of a large series of primary tumors.
Identified are six molecular subgroups of medulloblastoma, each with a unique combination of numerical and structural chromosomal aberrations that globally influence mRNA and miRNA expression. We reveal the relative contribution of each subgroup to clinical outcome as a whole and show that a previously unidentified molecular subgroup, characterized genetically by c-MYC copy number gains and transcriptionally by enrichment of photoreceptor pathways and increased miR-183-96-182 expression, is associated with significantly lower rates of event-free and overall survivals. Our results detail the complex genomic heterogeneity of medulloblastomas and identify a previously unrecognized molecular subgroup with poor clinical outcome for which more effective therapeutic strategies should be developed.
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| Overall design |
We profiled the mRNA transcriptome of 194 medulloblastomas and performed high-density single nucleotide polymorphism array and miRNA analysis on 115 and 98 of these, respectively. Non-negative matrix factorization-based clustering of mRNA expression data was used to identify molecular subgroups of medulloblastoma; DNA copy number, miRNA profiles, and clinical outcomes were analyzed for each. We additionally validated our findings in three previously published independent medulloblastoma data sets.
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| Contributor(s) |
Cho Y, Tsherniak A, Tamayo P, Santagata S, Ligon A, Creulich H, Berhoukim R, Amani V, Goumnerova L, Eberhart CG, Lau CC, Olson JM, Gilbertson RJ, Gajjar A, Delattre O, Kool M, Ligon K, Meyerson M, Mesirov JP, Pomeroy SL |
| Citation(s) |
21098324 |
| Submission date |
May 02, 2022 |
| Last update date |
Aug 02, 2022 |
| Contact name |
Jill P Mesirov |
| Organization name |
University of California, San Diego
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| Department |
Medicine
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| Street address |
9500 Gilman Drive
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| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
| GPL3921 |
[HT_HG-U133A] Affymetrix HT Human Genome U133A Array |
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| Samples (214)
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| Relations |
| BioProject |
PRJNA834075 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE202043_JCO.clinical_annot.xls.gz |
30.0 Kb |
(ftp)(http) |
XLS |
| GSE202043_RAW.tar |
542.8 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE202043_cho.expression.gct.gz |
35.8 Mb |
(ftp)(http) |
GCT |
| GSE202043_sample_list.xlsx |
25.3 Kb |
(ftp)(http) |
XLSX |
| Processed data are available on Series record |
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