Characterizing clinical and genomic factors of IDH-wildtype glioblastoma Open Access

Abstract

Purpose: Glioblastomas (GBMs) are one of the most common types of malignant brain tumor, and are typically associated with poor survival outcomes. Over the past decade, research has stratified GBMs into two categories based on their isocitrate dehydrogenase (IDH) mutational status. IDH-mutations have become a widely accepted marker for better prognosis in GBM. However, approximately 90% of GBMs are marked as IDH-wildtype (IDH-wt). Thus, identification and characterization of the clinical and genomic factors of IDH-wildtype GBM is necessary to analyze their significance for prognostic implications.

Methods: We collected data for 204 patients in the Emory Healthcare system that had a pathological diagnosis of IDH-wt, and had undergone surgical resection. Patient charts were evaluated based on their demographics, surgical outcomes, and pathological reports. Univariate and multivariate analyses were performed on our cohort following data collection.

Results: Overall, clinical factors significant for better prognosis included higher KPS score, fractionated radiation therapy, temozolomide, and avastin treatment. Based on univariate analysis, common IDH-wt GBM mutations such as EGFR amplification and PTEN loss had no significant correlation with overall survival or progression-free survival. Genomic factors that were most significant for better prognosis were 1p/19q co-deletion and chromosome 10q loss. Additional statistical analyses showed that copy neutral loss of heterozygosity (CN-LOH) was a significant prognostic factor for poor overall survival.

Conclusion: Collectively, our results indicate that there are a wide variety of genomic mutations in IDH-wt GBMs, providing a basis for identifying potential chromosomal mutations that may be significant for tumor progression and potential therapeutic effects.

Table of Contents

Introduction .................................................................................................................................... 1

Methods ........................................................................................................................................ 13

Results .......................................................................................................................................... 16

Discussion..................................................................................................................................... 21

Conclusion ................................................................................................................................... 33

References .................................................................................................................................... 35

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Genetics Biology, Neuroscience
Keyword	overall survival WHO grade IV glioma genomic mutations isocitrate dehydrogenase mutations IDH-wildtype progression-free survival prognostic factors glioblastoma
Committee Chair / Thesis Advisor	Hoang, Kimberly, Emory University
Committee Members	Hue, Gillian, Emory University Martin, Michael, Emory University

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