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Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma.
Magill, Stephen T; Vasudevan, Harish N; Seo, Kyounghee; Villanueva-Meyer, Javier E; Choudhury, Abrar; John Liu, S; Pekmezci, Melike; Findakly, Sarah; Hilz, Stephanie; Lastella, Sydney; Demaree, Benjamin; Braunstein, Steve E; Bush, Nancy Ann Oberheim; Aghi, Manish K; Theodosopoulos, Philip V; Sneed, Penny K; Abate, Adam R; Berger, Mitchel S; McDermott, Michael W; Lim, Daniel A; Ullian, Erik M; Costello, Joseph F; Raleigh, David R.
Afiliación
  • Magill ST; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Vasudevan HN; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Seo K; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Villanueva-Meyer JE; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Choudhury A; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • John Liu S; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Pekmezci M; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Findakly S; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Hilz S; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Lastella S; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Demaree B; Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Braunstein SE; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Bush NAO; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Aghi MK; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Theodosopoulos PV; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Sneed PK; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Abate AR; Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Berger MS; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • McDermott MW; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Lim DA; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Ullian EM; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Costello JF; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 94143, USA.
  • Raleigh DR; Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California San Francisco, San Francisco, CA, 94143, USA.
Nat Commun ; 11(1): 4803, 2020 09 23.
Article en En | MEDLINE | ID: mdl-32968068
ABSTRACT
Meningiomas are the most common primary intracranial tumors, but the molecular drivers of meningioma tumorigenesis are poorly understood. We hypothesized that investigating intratumor heterogeneity in meningiomas would elucidate biologic drivers and reveal new targets for molecular therapy. To test this hypothesis, here we perform multiplatform molecular profiling of 86 spatially-distinct samples from 13 human meningiomas. Our data reveal that regional alterations in chromosome structure underlie clonal transcriptomic, epigenomic, and histopathologic signatures in meningioma. Stereotactic co-registration of sample coordinates to preoperative magnetic resonance images further suggest that high apparent diffusion coefficient (ADC) distinguishes meningioma regions with proliferating cells enriched for developmental gene expression programs. To understand the function of these genes in meningioma, we develop a human cerebral organoid model of meningioma and validate the high ADC marker genes CDH2 and PTPRZ1 as potential targets for meningioma therapy using live imaging, single cell RNA sequencing, CRISPR interference, and pharmacology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Imagen por Resonancia Magnética / Heterogeneidad Genética / Perfilación de la Expresión Génica / Neoplasias Meníngeas Límite: Aged / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Imagen por Resonancia Magnética / Heterogeneidad Genética / Perfilación de la Expresión Génica / Neoplasias Meníngeas Límite: Aged / Female / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos