Cell lineage-based stratification for glioblastoma Journal Article


Authors: Wang, Z.; Sun, D.; Chen, Y. J.; Xie, X.; Shi, Y.; Tabar, V.; Brennan, C. W.; Bale, T. A.; Jayewickreme, C. D.; Laks, D. R.; Alcantara Llaguno, S.; Parada, L. F.
Article Title: Cell lineage-based stratification for glioblastoma
Abstract: Wang et al. identify lineage-specific subtypes in mouse and human glioblastoma that harbor distinct functional properties and therapeutic vulnerabilities, highlighting the role of cell lineage in glioblastoma and providing a classification system for future clinical investigations. © 2020 Elsevier Inc. Glioblastoma, the predominant adult malignant brain tumor, has been computationally classified into molecular subtypes whose functional relevance remains to be comprehensively established. Tumors from genetically engineered glioblastoma mouse models initiated by identical driver mutations in distinct cells of origin portray unique transcriptional profiles reflective of their respective lineage. Here, we identify corresponding transcriptional profiles in human glioblastoma and describe patient-derived xenografts with species-conserved subtype-discriminating functional properties. The oligodendrocyte lineage-associated glioblastoma subtype requires functional ERBB3 and harbors unique therapeutic sensitivities. These results highlight the importance of cell lineage in glioblastoma independent of driver mutations and provide a methodology for functional glioblastoma classification for future clinical investigations. © 2020 Elsevier Inc.
Keywords: mitogen activated protein kinase; protein kinase b; adult; controlled study; human tissue; protein phosphorylation; gene mutation; human cell; nonhuman; animal cell; mouse; animal tissue; gene expression profiling; epidermal growth factor receptor; epidermal growth factor receptor 2; animal experiment; animal model; genetic transcription; neural stem cell; dasatinib; protein tyrosine kinase; cell lineage; messenger rna; glioblastoma; epidermal growth factor receptor 3; drug sensitivity; transcriptome; cell of origin; intracellular signaling; mouse model; neu differentiation factor; oligodendroglia; molecular subtype; transcription factor sox9; molecular classification; pdx; transcription factor sox10; gbm; erbb3; human; female; priority journal; article; oligodendrocyte lineage cell; tucatinib
Journal Title: Cancer Cell
Volume: 38
Issue: 3
ISSN: 1535-6108
Publisher: Cell Press  
Date Published: 2020-09-14
Start Page: 366
End Page: 379.e8
Language: English
DOI: 10.1016/j.ccell.2020.06.003
PUBMED: 32649888
PROVIDER: scopus
PMCID: PMC7494533
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Viviane S Tabar
    160 Tabar
  2. Cameron Brennan
    183 Brennan
  3. Luis F Parada
    19 Parada
  4. Yufeng Shi
    4 Shi
  5. Zilai Wang
    6 Wang
  6. Daochun Sun
    10 Sun
  7. Xuanhua Xie
    8 Xie
  8. Dan R Laks
    5 Laks
  9. Tejus Bale
    31 Bale
  10. Yu-Jung Chen
    2 Chen