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

Autor: Sydney Lastella, David R. Raleigh, Stephen T. Magill, Harish N. Vasudevan, Joseph F. Costello, Philip V. Theodosopoulos, Manish K. Aghi, Benjamin Demaree, Daniel A. Lim, Javier Villanueva-Meyer, Penny K. Sneed, Adam R. Abate, Steve Braunstein, Melike Pekmezci, Sarah Findakly, Michael W. McDermott, Kyounghee Seo, Abrar Choudhury, S. John Liu, Stephanie Hilz, Mitchel S. Berger, Erik M. Ullian, Nancy Ann Oberheim Bush
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Epigenomics
Receptor-Like Protein Tyrosine Phosphatases
General Physics and Astronomy
medicine.disease_cause
Gene regulatory networks
Transcriptome
0302 clinical medicine
Meningeal Neoplasms
2.1 Biological and endogenous factors
Aetiology
lcsh:Science
Cancer
Multidisciplinary
medicine.diagnostic_test
Brain Neoplasms
Receptor-Like Protein Tyrosine Phosphatases
Class 5
Genomics
Cadherins
Magnetic Resonance Imaging
CD
Female
Biotechnology
Cerebral organoid
Genetic Markers
Tumour heterogeneity
Science
Biology
General Biochemistry
Genetics and Molecular Biology
Article
Meningioma
03 medical and health sciences
Genetic Heterogeneity
Rare Diseases
Cancer epigenetics
Antigens
CD
Genetics
medicine
otorhinolaryngologic diseases
Humans
Antigens
neoplasms
Aged
Genetic heterogeneity
Gene Expression Profiling
Human Genome
Neurosciences
Magnetic resonance imaging
General Chemistry
medicine.disease
Class 5
Brain Disorders
nervous system diseases
Brain Cancer
CNS cancer
030104 developmental biology
Diffusion Magnetic Resonance Imaging
Cancer research
lcsh:Q
Carcinogenesis
030217 neurology & neurosurgery
Zdroj: Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020)
Nature Communications
Nature communications, vol 11, iss 1
ISSN: 2041-1723
DOI: 10.1038/s41467-020-18582-7
Popis: 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.
Meningiomas are heterogeneous tumours. Here, the authors analysed genetic, epigenetic, and transcriptomic features across spatially-distinct meningioma samples to identify molecular programs underlying tumorigenesis that can be detected preoperatively using magnetic resonance imaging.
Databáze: OpenAIRE
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