Genetic and clinical characteristics of primary and secondary glioblastoma is associated with differential molecular subtype distribution
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Rui Li1,*, Hailin Li1,*, Wei Yan1, Pei Yang2,4, Zhaoshi Bao2,4, Chuanbao Zhang2,4, Tao Jiang2,3,4 and Yongping You1
1 Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
2 Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
3 Beijing Institute for Brain Disorders, Brain Tumor Center, Beijing, China
4 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
* These authors have contributed equally to this work
Yongping You, email:
Keywords: Primary glioblastomas, Secondary glioblastomas, Molecular subtypes, Whole transcriptome sequencing
Received: December 05, 2014 Accepted: January 21, 2015 Published: January 31, 2015
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.
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