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Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective.
Mathur, Radhika; Wang, Qixuan; Schupp, Patrick G; Nikolic, Ana; Hilz, Stephanie; Hong, Chibo; Grishanina, Nadia R; Kwok, Darwin; Stevers, Nicholas O; Jin, Qiushi; Youngblood, Mark W; Stasiak, Lena Ann; Hou, Ye; Wang, Juan; Yamaguchi, Takafumi N; Lafontaine, Marisa; Shai, Anny; Smirnov, Ivan V; Solomon, David A; Chang, Susan M; Hervey-Jumper, Shawn L; Berger, Mitchel S; Lupo, Janine M; Okada, Hideho; Phillips, Joanna J; Boutros, Paul C; Gallo, Marco; Oldham, Michael C; Yue, Feng; Costello, Joseph F.
Affiliation
  • Mathur R; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Wang Q; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Schupp PG; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Nikolic A; Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, AB.
  • Hilz S; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Hong C; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Grishanina NR; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Kwok D; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Stevers NO; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Jin Q; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Youngblood MW; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Stasiak LA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Hou Y; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Wang J; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Yamaguchi TN; Department of Human Genetics, University of California, Los Angeles, Los Angees, CA, USA.
  • Lafontaine M; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Shai A; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Smirnov IV; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Solomon DA; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
  • Chang SM; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Hervey-Jumper SL; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Berger MS; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Lupo JM; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Okada H; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Phillips JJ; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Boutros PC; Department of Human Genetics, University of California, Los Angeles, Los Angees, CA, USA.
  • Gallo M; Department of Biochemistry & Molecular Biology, University of Calgary, Calgary, AB; Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
  • Oldham MC; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
  • Yue F; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: yue@northwestern.edu.
  • Costello JF; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA. Electronic address: joseph.costello@ucsf.edu.
Cell ; 187(2): 446-463.e16, 2024 01 18.
Article in En | MEDLINE | ID: mdl-38242087
ABSTRACT
Treatment failure for the lethal brain tumor glioblastoma (GBM) is attributed to intratumoral heterogeneity and tumor evolution. We utilized 3D neuronavigation during surgical resection to acquire samples representing the whole tumor mapped by 3D spatial coordinates. Integrative tissue and single-cell analysis revealed sources of genomic, epigenomic, and microenvironmental intratumoral heterogeneity and their spatial patterning. By distinguishing tumor-wide molecular features from those with regional specificity, we inferred GBM evolutionary trajectories from neurodevelopmental lineage origins and initiating events such as chromothripsis to emergence of genetic subclones and spatially restricted activation of differential tumor and microenvironmental programs in the core, periphery, and contrast-enhancing regions. Our work depicts GBM evolution and heterogeneity from a 3D whole-tumor perspective, highlights potential therapeutic targets that might circumvent heterogeneity-related failures, and establishes an interactive platform enabling 360° visualization and analysis of 3D spatial patterns for user-selected genes, programs, and other features across whole GBM tumors.
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Full text: 1 Database: MEDLINE Main subject: Brain Neoplasms / Glioblastoma / Models, Biological Limits: Humans Language: En Year: 2024 Type: Article
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PubMed Links
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Full text: 1 Database: MEDLINE Main subject: Brain Neoplasms / Glioblastoma / Models, Biological Limits: Humans Language: En Year: 2024 Type: Article