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NPJ Genom Med. 2017;2. pii: 15. doi: 10.1038/s41525-017-0014-7. Epub 2017 Apr 26.

Genomic landscape of high-grade meningiomas.

Author information

1
Center for Skull Base and Pituitary Surgery, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
3
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
4
Division of Neuropathology, Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
5
Research Center, King Fahad Medical City, Riyadh, Saudi Arabia.
6
The Saudi Human Genome Project Lab, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
7
Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
8
Department of Surgery, The University of Chicago, Chicago, IL, USA.
9
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
10
Computer Technologies Department, ITMO University, Saint Petersburg, Russia.
11
Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA, USA.
12
Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
13
Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, USA.
14
Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
15
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Abstract

High-grade meningiomas frequently recur and are associated with high rates of morbidity and mortality. To determine the factors that promote the development and evolution of these tumors, we analyzed the genomes of 134 high-grade meningiomas and compared this information with data from 587 previously published meningiomas. High-grade meningiomas had a higher mutation burden than low-grade meningiomas but did not harbor any statistically significant mutated genes aside from NF2. High-grade meningiomas also possessed significantly elevated rates of chromosomal gains and losses, especially among tumors with monosomy 22. Meningiomas previously treated with adjuvant radiation had significantly more copy number alterations than radiation-induced or radiation-naïve meningiomas. Across serial recurrences, genomic disruption preceded the emergence of nearly all mutations, remained largely uniform across time, and when present in low-grade meningiomas, correlated with subsequent progression to a higher grade. In contrast to the largely stable copy number alterations, mutations were strikingly heterogeneous across tumor recurrences, likely due to extensive geographic heterogeneity in the primary tumor. While high-grade meningiomas harbored significantly fewer overtly targetable alterations than low-grade meningiomas, they contained numerous mutations that are predicted to be neoantigens, suggesting that immunologic targeting may be of therapeutic value.

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