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Series GSE49265 Query DataSets for GSE49265
Status Public on Feb 01, 2016
Title Progression from low- to high-grade astrocytoma is characterized by transcriptomal heterogeneity and genomic number copy alterations (part 1)
Organism Mus musculus
Experiment type Expression profiling by array
Summary We used genetically-engineered mice (GEM) to target constitutive RTK effector pathway (KrasG12D and/or Pten deletion) mutations in G1/S checkpoint-defective adult mouse astrocytes. Genetic lineage tracing showed that these mutations potentiated tumor initiation in cortical, diencephalic, brainstem, and olfactory bulb astrocytes, producing low-grade astrocytomas (LGA). LGA lacked copy number abnormalities (CNA), but showed oncogenic driver- and astrocyte location-specific transcriptome profiles, suggesting that both driver mutations and cellular origin contribute to LGA genomic heterogeneity. Progression to high-grade astrocytomas (HGA) occurred stochastically, in part through location-specific acquisition of CNA. HGA transcriptomes were heterogeneous and consisted of three subtypes that were also evident in GEM HGA with different oncogenic drivers and cellular origins. HGA subtypes expressing immune/invasion, proliferation, and neuronal genes mimicked human mesenchymal, proneural, and neural GBM, respectively. HGA subtypes also expressed distinct neural lineage signatures and were correlated with astrocyte location, but not oncogenic driver mutations. These results suggest that oncogenic drivers influence LGA subtype and that regional astrocyte identity and progression-acquired CNA contribute strongly to HGA transcriptomal heterogeneity. Defining tumor-initiating and progression-acquired mutations and the cells in which they occur would facilitate molecular classification and development of molecularly targeted strategies to manage GBM.
Overall design 78 olfactory bulb and forebrain samples of various genotypes showed oncogenic driver- and astrocyte location-specific transcriptome profiles
Contributor(s) Vitucci M, Miller CR
Citation(s) 28398584
Submission date Jul 26, 2013
Last update date Jun 15, 2017
Contact name Ryan Miller
Phone 919-966-4333
Organization name University of North Carolina
Department Pathology
Street address 6109B NRB CB 7250
City Chapel HIll
State/province North Carolina
ZIP/Postal code 27599
Country USA
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (78)
GSM1196145 215534_Forebrain_TRPnull
GSM1196146 219596_Forebrain_TRPhet
GSM1196147 215697_Forebrain_TRPnull
This SubSeries is part of SuperSeries:
GSE49269 Progression from low- to high-grade astrocytoma is characterized by transcriptomal heterogeneity and genomic number copy alterations
BioProject PRJNA213446

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
GSE49265_RAW.tar 1.2 Gb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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