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Series GSE30530 Query DataSets for GSE30530
Status Public on Sep 01, 2011
Title MYCN-MB with MYCN amplification
Organism Homo sapiens
Experiment type Expression profiling by array
Summary BACKGROUND Focal high-level amplifications of MYC define a subset of high-risk medulloblastoma patients. However, the prognostic role of MYCN oncogene amplification remains less clear. We aimed to evaluate the prognostic value of this alteration alone and in combination with biological modifiers in a large cohort of 67 pediatric medulloblastomas with MYCN amplification (MYCN-MB). METHODS Twenty-one MYCN-MB with MYCN amplication and 56 MYCN-MB were respectively examined using either gene expression profiling and array-CGH, or immunohistochemical analysis and FISH. All 67 tumors were further subject to mutational analyses. Semi non-negative matrix factorization–based and unsupervised hierarchical clustering methods were used to identify biological groups. We compared molecular, clinical, and prognostic characteristics both within biological MYCN-MB groups and with non-amplified tumors. RESULTS Transcriptomic analysis of this large cohort of MYCN-MBs demonstrated a significant enrichment of MYCN-MB in the SHH and group D variants. Further substantiating this biological dichotomy of MYCN-MB, respective group affiliations were also accompanied by variant-specific cytogenetic aberrations including deletion of 9q in the SHH variant, and gain of 7q and isochromosome 17q/17q gain in MYCN-MBs clustering with group D tumors. Among clinically relevant variables, SHH subtype and 10q loss for Non-SHH tumors comprised the most powerful markers of favorable prognosis in MYCN-MB. CONCLUSION We demonstrate considerable heterogeneity within MYCN-MB in terms of genetics, tumor biology, and clinical outcome. Thus, assessment of disease group and 10q copy-number status may improve risk stratification of this group and may delineate MYCN-MB with the same dismal prognosis as MYC amplified tumors. Furthermore, based on the enrichment of MYCN and GLI2 amplifications in SHH-driven medulloblastoma, amplification of these downstream signaling intermediates should be excluded before a patient is enrolled into a clinical trial using a Smoothened inhibitor.
 
Overall design Fresh frozen tumor material was collected during tumor resection. Gene expression profiles illustrate distinct expression pattern at diagnosis.

This submission represents the gene expression component of the study only
 
Contributor(s) Korshunov A, Remke M, Kool M, Hielscher T, Northcott PA, Williamson D, Witt H, Jones DT, Ryzhova M, Pfaff E, Cho Y, Wittmann A, Weiss WA, Benner A, von Deimling A, Scheurlen W, Kulozik A, Clifford S, Collins VP, Westermann F, Taylor MD, Lichter P, Pfister SM
Citation(s) 22160402
Submission date Jul 08, 2011
Last update date Jan 23, 2019
Contact name Marc Remke
E-mail(s) marcremke@gmail.com
Organization name The Hospital for Sick Children
Department Laboratory Medicine and Pathobiology
Street address 555 University Ave. Rm 1504
City Toronto
ZIP/Postal code M5G 1X8
Country Canada
 
Platforms (1)
GPL6480 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Probe Name version)
Samples (77)
GSM757036 MYCN amplification MB70
GSM757037 MYCN amplification MB835
GSM757038 MYCN amplification MB1165
Relations
BioProject PRJNA143309

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
GSE30530_RAW.tar 1013.8 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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