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Series GSE21140 Query DataSets for GSE21140
Status Public on Sep 14, 2010
Title Genomics of medulloblastoma identifies four distinct molecular variants
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Recent genomic approaches have suggested the existence of multiple distinct subtypes of medulloblastoma. We studied a large cohort of medulloblastomas to determine how many subgroups of the disease exist, how they differ, and the extent of overlap between subgroups. We determined gene expression profiles and DNA copy number aberrations for 103 primary medulloblastomas. Bioinformatic tools were used for class discovery of medulloblastoma subgroups based on the most informative genes in the dataset. Immunohistochemistry for subgroup-specific ‘signature’ genes was used to determine subgroup affiliation for 294 non-overlapping medulloblastomas on two independent tissue microarrays (TMAs). Multiple unsupervised analyses of transcriptional profiles identified four distinct, non-overlapping molecular variants: WNT, SHH, Group C, and Group D. Supervised analysis of these four subgroups revealed significant subgroup-specific demographics, histology, metastatic status, and DNA copy number aberrations. Immunohistochemistry for DKK1 (WNT), SFRP1 (SHH), NPR3 (Group C), and KCNA1 (Group D) could reliably and uniquely classify formalin fixed medulloblastomas in ~98% of cases. Group C patients (NPR3 +ve tumors) exhibited a significantly diminished progression free and overall survival irrespective of their metastatic status. Our integrative genomics approach to a large cohort of medulloblastomas has identified four disparate subgroups with distinct demographics, clinical presentation, transcriptional profiles, genetic abnormalities, and clinical outcome. Medulloblastomas can be reliably assigned to subgroups through immunohistochemistry, thereby making medulloblastoma sub-classification widely available. Future research on medulloblastoma and the development of clinical trials should take into consideration these four distinct types of medulloblastoma.
 
Overall design A total of 103 primary medulloblastoma specimens were profiled by Affymetrix exon array and gene-level analysis was performed.
 
Contributor(s) Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, Bouffet E, Clifford SC, Hawkins CE, French P, Rutka JT, Pfister S, Taylor MD
Citation(s) 20823417
Submission date Mar 30, 2010
Last update date Feb 18, 2019
Contact name Paul A. Northcott
E-mail(s) panorthcott@gmail.com
Organization name German Cancer Research Center (DKFZ)
Street address Im Neuenheimer Feld 280
City HEIDELBERG
ZIP/Postal code 69120
Country Germany
 
Platforms (1)
GPL5175 [HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version]
Samples (103)
GSM529305 Primary medulloblastoma MDT-MB-1
GSM529306 Primary medulloblastoma MDT-MB-101
GSM529307 Primary medulloblastoma MDT-MB-103
Relations
BioProject PRJNA126659

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE21140_RAW.tar 2.3 Gb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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