title: Genetic and clinical characteristics of primary and secondary glioblastoma is associated with differential molecular subtype distribution.
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.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: molecular subtypes; primary glioblastomas; secondary glioblastomas; whole transcriptome sequencing
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