Comprehensive portrait of recurrent glioblastoma multiforme in molecular and clinical characteristics

Rui Li,Yanwei Liu,Yongping You,Qi Hu,Xiefeng Wang,Xincheng Chen,Wei Yan

doi:10.18632/oncotarget.5038

Abstract

Glioblastoma multiforme is the most common primary malignant brain tumor in adults. In addition to poor response to treatment, a high recurrence rate contributes to the poor prognosis. The purpose of this study was to investigate the genetical and clinical characteristics of recurrent glioblastoma. We used whole transcriptome sequencing data to examine the distribution of molecular subtypes and gene signatures in 22 recurrent glioblastoma taken from the Chinese population, and further analyzed biological progression of the tumors, when compared with primary glioblastoma. The proportion of the classical subtype in recurrent ones (22%) was lower than that in primary glioblastoma (36%). The frequency of IDH1 mutations in recurrent glioblastomas was nearly twice that in primary glioblastomas. TP53 mutations were fewer in proneural recurrent glioblastomas (20%) but frequent in classical recurrent glioblastomas (80%). The most common sites of recurrent glioblastomas were the temporal lobe (41%). In patients diagnosed with recurrent glioblastoma multiforme, 64% were younger than 50 years. Gene set enrichment analysis revealed that chromatin fracture, repair, and remodeling genes were enriched in recurrent glioblastoma. Our results highlight the differences in clinical features, molecular subtypes and gene alterations between primary and recurrent glioblastoma and may be helpful for targeted therapy for recurrent glioblastoma.

Highlights

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults
Our findings provide a comprehensive portrait of gene alterations, clinical features and gene set enrichment in primary and recurrent GBM, which could be helpful in determining the direction of potential targeted drug therapy
Samples identified as being of the neural subtype made up 8% of primary GBM and 9% of recurrent GBM

Summary

Introduction

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. The high recurrence rate found in patients with GBM is a major clinical challenge. In addition to a high rate of recurrence, the appearance of new genetic mutations and malignant phenotypes in the process of recurrence increases the difficulty of treatment for recurrent GBM [17, 18]. A comprehensive portrait of the genetic alterations, age distribution, tumor localization and other clinical features in primary and recurrent GBM is needed to better classify tumor profiles. This could lead to an understanding of the characteristics of recurrent GBM, and suggest potential targets for personalized therapeutic strategies

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