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Expression profiling of lower-grade diffuse astrocytic glioma

UID: 11221

Author(s): Huse, Jason T.* * MSK affiliated

Description
Summary from GEO:

"Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in the understanding of glioblastoma (WHO IV), its most malignant subtype, lower-grade (WHO II and III) glioma variants remain comparatively understudied, especially in light of their notably variable clinical behavior. To examine the foundations of this heterogeneity, we performed multidimensional molecular profiling, including global transcriptional analysis, on 101 lower-grade diffuse astrocytic gliomas collected at our own institution, and validated our findings using publically available gene expression and copy number data from large independent patient cohorts. We found that IDH mutational status delineated molecularly and clinically distinct glioma subsets, with IDH mutant (IDH mt) tumors exhibiting TP53 mutations, PDGFRA overexpression, and prolonged survival, and IDH wild-type (IDH wt) tumors exhibiting EGFR amplification, PTEN loss, and unfavorable disease outcome. Furthermore, global expression profiling revealed three robust molecular subclasses within lower-grade diffuse astrocytic gliomas, two of which were predominantly IDH mt and one almost entirely IDH wt. IDH mt subclasses were distinguished from each other on the basis of TP53 mutations, DNA copy number abnormalities, and links to distinct stages of neurogenesis in the subventricular zone (SVZ). This latter finding implicates discrete pools of neuroglial progenitors as cells of origin for the different subclasses of IDH mt tumors. In summary, we have elucidated molecularly distinct subclasses of lower-grade diffuse astrocytic glioma that dictate clinical behavior and demonstrate fundamental associations with both IDH mutational status and neuroglial developmental stage."

Overall design from GEO:

"80 tumor samples, one normal tissue sample (brain)"
Subject of Study
Homo sapiens
Subject(s)
Brain Stem Neoplasms
Gene Expression
Glioma
Mutation
Neurogenesis
OncoTree Cancer Type(s)
Diffuse Glioma
Access via GEO


Accession #: GSE35158

Access via BioProject


Accession #: PRJNA150783

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus and BioProject databases provides open access to these files.
Associated Publications
Gorovets D, Kannan K, Shen R, Kastenhuber E, Islamdoust N, Campos C, Pentsova E, Heguy A, Jhanwar S, Mellinghoff I, Chan T, Huse J. IDH mutation and neuroglial developmental features define clinically distinct subclasses of lower grade diffuse astrocytic glioma. Clinical Cancer Research. 2012; 18(9):2490-2501.
Equipment Used
Illumina HumanHT-12 V4.0 expression beadchip
Dataset Format(s)
TXT
Dataset Size
37.6 MB
Data Catalog Record Updated
2024-04-09