A Brain Penetrant Mutant IDH1 Inhibitor Provides In Vivo Survival Benefit
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA415191 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6388470.fastq.gz | Fastqsanger.gz | |||
| SRR6388470_1.fastq.gz | Fastqsanger.gz | |||
| SRR6388470_2.fastq.gz | Fastqsanger.gz | |||
| SRR6388480.fastq.gz | Fastqsanger.gz | |||
| SRR6388480_1.fastq.gz | Fastqsanger.gz |
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Project description:Astrocytoma, oligodendroglioma, oligoastrocytoma, and ependymoma are the main histologic subtypes of glioma. The molecular character of these subtypes has profound implications for understanding their causes and treatment. We describe the epigenetic landscape of these tumor types using novel DNA methylation profiling tools. There is a robust association of methylation profile with tumor histology and IDH1 mutation status. Furthermore, tumors with IDH1 mutation independently predict a tumor hypermethylator phenotype, histology, TP53 mutation status, patient age, and survival. Integrating tumor epigenetic and genetic alterations, this work provides a critical step toward better defining the somatic nature of glioma which will have great potential to impact clinical approaches to disease. This work provides an important step forward in classification of malignant brain tumors using DNA methylation profiling, integrating knowledge regarding IDH1 mutation in gliomas. The epigenetic homogeneity of the IDH1 mutant subclass despite histologic diversity implies that IDH1 mutation is a “driver” or functional determinant of a distinct DNA methylation phenotype, suggesting a novel role for an altered metabolic profile in the brain. This association occurs across histologic subtypes and demonstrates a clear relationship between genetic alteration and epigenetic profile. Fresh frozen tumor tissues were obtained from the University of California San Francisco (UCSF) Brain Tumor Research Center tissue bank with appropriate institutional review board approval. Tumors were diagnosed between 1990 and 2003. Tumor samples were defined as secondary GBM if the patients had prior histological diagnosis of a low-grade glioma. Tumors had previously been reviewed by UCSF neuropathologists to assign histologic subtype and grade. Normal brain tissue samples were from cancer-free patients who underwent temporal lobe resection as treatment for epilepsy at UCSF.
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