Integrative Genomic Analysis of Medulloblastoma Identifies a Molecular Subgroup That Drives Poor Clinical Outcome
Boston Children's Hospital · Johns Hopkins University · +8 more institutions
Abstract
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.
Citation impact
- FWCI
- 24.54
- Percentile
- 100%
- References
- 38
Authors
20- YCYoon-Jae Cho
Boston Children's Hospital, Johns Hopkins University, Baylor College of Medicine, University of Washington, University Medical Center, Amsterdam UMC Location University of Amsterdam, Fred Hutch Cancer Center, Dana-Farber Cancer Institute, Cancer Research Center, Children's Cancer Center
- ATAviad Tsherniak
Boston Children's Hospital, Johns Hopkins University, Baylor College of Medicine, University of Washington, University Medical Center, Amsterdam UMC Location University of Amsterdam, Fred Hutch Cancer Center, Dana-Farber Cancer Institute, Cancer Research Center, Children's Cancer Center
- PTPablo Tamayo
Boston Children's Hospital, Johns Hopkins University, Baylor College of Medicine, University of Washington, University Medical Center, Amsterdam UMC Location University of Amsterdam, Fred Hutch Cancer Center, Dana-Farber Cancer Institute, Cancer Research Center, Children's Cancer Center
- SSSandro Santagata
Boston Children's Hospital, Johns Hopkins University, Baylor College of Medicine, University of Washington, University Medical Center, Amsterdam UMC Location University of Amsterdam, Fred Hutch Cancer Center, Dana-Farber Cancer Institute, Cancer Research Center, Children's Cancer Center
- AHAzra H. Ligon
Boston Children's Hospital, Johns Hopkins University, Baylor College of Medicine, University of Washington, University Medical Center, Amsterdam UMC Location University of Amsterdam, Fred Hutch Cancer Center, Dana-Farber Cancer Institute, Cancer Research Center, Children's Cancer Center
Topics & keywords
- Medulloblastoma
- microRNA
- Transcriptome
- Computational biology
- Biology
- Genetic heterogeneity
- Copy-number variation
- Oncology
- No poverty