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Abstract Details

Transcriptomic Analysis of Rapid Glioblastoma Progressors
Neuro-oncology
S14 - Neuro-oncology (2:48 PM-3:00 PM)
010
To define mRNA expression patterns predictive of poor response to treatment in glioblastoma

Despite modern therapeutic advances, the median overall survival for patients with glioblastoma remains approximately 14 months.  A subset of patients progresses much more rapidly while about 1-2% of patients survive beyond 3 years from diagnosis. Yet predicting which patients are likely to progress rapidly versus slowly remains challenging.  At the transcriptomic level, database analyses have demonstrated the importance of RNA splicing variants and RNA binding protein interactions in glioblastoma pathogenesis. In this work, we explore whether mRNA expression patterns in newly diagnosed glioblastoma patients can be used to predict response to standard therapy.

We compare mRNA expression data with clinical outcomes from the publicly-available Cancer Genome Atlas (TCGA).  These data include 78 patients with time-to-death data, of whom 10 survived less than 100 days from diagnosis and 38 survived more than 1 year from diagnosis.  We analyzed differences in mRNA expression profiles between these two groups. We are additionally in the process of accruing transcriptome data for a clinically-annotated cohort of about 300 glioblastoma patients treated at our institution.

Using TCGA data, we find that there are significant differences in gene expression profiles between rapid progressors and those who survive longer than 1 year.  Gene set enrichment analysis shows underexpression of markers of immune activation and cell cycle regulation, and overexpression of RAS signalling. This analysis is limited by the lack of clinical annotation available in TCGA and the small number of patients.  


These results demonstrate that mRNA expression patterns recapitulate expected markers of glioblastoma progression.  They motivate our ongoing efforts to uncover novel transcriptomic signatures in a large clinically-annotated dataset.  


Authors/Disclosures
Justin T. Low, MD, PhD (Duke University School of Medicine)
PRESENTER
Dr. Low has nothing to disclose.
No disclosure on file