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. 2015 Mar 30;6(9):7318-24.
doi: 10.18632/oncotarget.3440.

Genetic and clinical characteristics of primary and secondary glioblastoma is associated with differential molecular subtype distribution

Rui Li  1 , Hailin Li  1 , Wei Yan  1 , Pei Yang  2   3 , Zhaoshi Bao  2   3 , Chuanbao Zhang  2   3 , Tao Jiang  2   4   3 , Yongping You  1
Affiliations

Genetic and clinical characteristics of primary and secondary glioblastoma is associated with differential molecular subtype distribution

Rui Li et al. Oncotarget. .

Abstract

Glioblastoma multiforme (GBM) is classified into primary (pGBM) or secondary (sGBM) based on clinical progression. However, there are some limits to this classification for insight into genetically and clinically distinction between pGBM and sGBM. The aim of this study is to characterize pGBM and sGBM associating with differential molecular subtype distribution. Whole transcriptome sequencing data was used to assess the distribution of molecular subtypes and genetic alterations in 88 pGBM and 34 sGBM in a Chinese population-based cohort, and the biological progression and prognostic impact were analyzed by combining clinical information. Forty-one percentage of pGBM were designated as Mesenchymal subtype, while only 15% were the Proneural subtype. However, sGBM displayed the opposite ratio of Mesenchymal (15%) and Proneural (44%) subtypes. Mutations in isocitrate dehydrogenase-1 (IDH1) were found to be highly concentrated in the Proneural subtypes. In addition, patients with sGBM were 10 years younger on average than those with pGBM, and exhibited clinical features of shorter overall survival and frontal lobe tumor location tendency. Furthermore, in sGBM, gene sets related to malignant progression were found to be enriched. Overall, these results reveal the intrinsic distinction between pGBM and sGBM, and provide insight into the genetic and clinical attributes of GBM.

Keywords: molecular subtypes; primary glioblastomas; secondary glioblastomas; whole transcriptome sequencing.

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Conflict of interest statement

CONFLICT OF INTEREST

All authors report no conflicts of interest relevant to this article.

Figures

Figure 1
Figure 1. Distribution of molecular subtypes and genetic alteration signatures in pGBM and sGBM
Distribution and correlation between GBM molecular subtypes (Proneural, Neural, Classical and Mesenchymal), IDH1 mutation, TP53 mutation, EGFR mutation and ATRX mutation in pGBM and sGBM. Molecular subtypes and genetic alterations are indicated in different colors.
Figure 2
Figure 2. Presence of gene sets related to biological processes analyzed by GSEA
(A) Gene sets related to biological processes in pGBM; (B) Gene sets related to biological processes in sGBM.
Figure 3
Figure 3. Kaplan–Meier analysis of overall survivals of patients with GBM
(A) Overall survival of patients with pGBM and sGBM; (B) Overall survivals of patients with or without IDH1 mutation in pGBM and sGBM; (C) Overall survivals of patients with Proneural, Neural, Classical and Mesenchymal subtypes.
Figure 4
Figure 4. Age distribution of patients with GBM
(A) Distribution of molecular subtypes in pGBM and sGBM; (B) Age distribution of patients with molecular and clinical subtypes of GBM; (C) Age distribution of patients with four molecular subtypes of GBM. *, P<0.05; **, P<0.01; ****, P<0.0001.
See this image and copyright information in PMC

References

    1. Ohgaki H, Kleihues P. Epidemiology and etiology of gliomas. Acta neuropathologica. 2005;109(1):93–108. - PubMed
    1. Peiffer J, Kleihues P. Hans-Joachim Scherer (1906-1945), pioneer in glioma research. Brain pathology. 1999;9(2):241–245. - PMC - PubMed
    1. Scherer HJ. Cerebral astrocytomas and their derivatives. Am. J Cancer. 1940;40:159–198.
    1. Yan W, Li R, Liu Y, Yang P, Wang Z, Zhang C, Bao Z, Zhang W, You Y, Jiang T. MicroRNA expression patterns in the malignant progression of gliomas and a 5-microRNA signature for prognosis. Oncotarget. 2014;5(24):12908–12915. - PMC - PubMed
    1. Balss J, Meyer J, Mueller W, Korshunov A, Hartmann C, von Deimling A. Analysis of the IDH1 codon 132 mutation in brain tumors. Acta neuropathologica. 2008;116(6):597–602. - PubMed

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