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.
Highlights
Glioblastoma multiforme (GBM) is the most lethal type of adult brain tumor, accounting for 60–70% of all gliomas
The majority of isocitrate dehydrogenase-1 (IDH1) mutations were clustered in Proneural subtypes in both primary glioblastoma (pGBM) and secondary glioblastoma (sGBM), whereas IDH2 mutation was absent in the whole cohort
Such alteration was mutually exclusive with IDH1 mutation and Epidermal growth factor receptor (EGFR) mutation, but co-occurred with TP53 mutation in pGBM
Summary
Glioblastoma multiforme (GBM) is the most lethal type of adult brain tumor, accounting for 60–70% of all gliomas. The median survival of patients with GBM is approximately 15 months [1]. GBM is divided into primary glioblastoma (pGBM), which progresses rapidly and has an absence of precursor lesions, and secondary glioblastoma (sGBM), which progresses as diffuse astrocytoma (WHO grade II) or anaplastic astrocytoma (WHO grade III) [2,3,4]. PGBM and sGBM display distinct clinical progression, they are histologically indistinguishable. Research efforts have focused on investigating GBM molecular profiles. The Cancer Genome Atlas (TCGA) Research Network described a robust gene expression-based molecular classification of GBM into Proneural, Neural, Classical and Mesenchymal subtypes [10]
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