Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma

Stephen T. Magill, Harish N. Vasudevan, Kyounghee Seo, Javier E. Villanueva-Meyer, Abrar Choudhury, S. John Liu, Melike Pekmezci, Sarah Findakly, Stephanie Hilz, Sydney Lastella, Benjamin Demaree, Steve E. Braunstein, Nancy Ann Oberheim Bush, Manish K. Aghi, Philip V. Theodosopoulos, Penny K. Sneed, Adam R. Abate, Mitchel S. Berger, Michael W. McDermott, Daniel A. Lim, Erik M. Ullian, Joseph F. Costello and David R. Raleigh ()
Additional contact information
Stephen T. Magill: University of California San Francisco
Harish N. Vasudevan: University of California San Francisco
Kyounghee Seo: University of California San Francisco
Javier E. Villanueva-Meyer: University of California San Francisco
Abrar Choudhury: University of California San Francisco
S. John Liu: University of California San Francisco
Melike Pekmezci: University of California San Francisco
Sarah Findakly: University of California San Francisco
Stephanie Hilz: University of California San Francisco
Sydney Lastella: University of California San Francisco
Benjamin Demaree: University of California San Francisco
Steve E. Braunstein: University of California San Francisco
Nancy Ann Oberheim Bush: University of California San Francisco
Manish K. Aghi: University of California San Francisco
Philip V. Theodosopoulos: University of California San Francisco
Penny K. Sneed: University of California San Francisco
Adam R. Abate: University of California San Francisco
Mitchel S. Berger: University of California San Francisco
Michael W. McDermott: University of California San Francisco
Daniel A. Lim: University of California San Francisco
Erik M. Ullian: University of California San Francisco
Joseph F. Costello: University of California San Francisco
David R. Raleigh: University of California San Francisco

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18582-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18582-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18582-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().