Genomic landscape of high-grade meningiomas View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-04-26

AUTHORS

Wenya Linda Bi, Noah F. Greenwald, Malak Abedalthagafi, Jeremiah Wala, Will J. Gibson, Pankaj K. Agarwalla, Peleg Horowitz, Steven E. Schumacher, Ekaterina Esaulova, Yu Mei, Aaron Chevalier, Matthew A. Ducar, Aaron R. Thorner, Paul van Hummelen, Anat O. Stemmer-Rachamimov, Maksym Artyomov, Ossama Al-Mefty, Gavin P. Dunn, Sandro Santagata, Ian F. Dunn, Rameen Beroukhim

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 595 previously published meningiomas. High-grade meningiomas had a higher mutation burden than low-grade meningiomas but did not harbor any significantly 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. More... »

PAGES

15

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41525-017-0014-7

    DOI

    http://dx.doi.org/10.1038/s41525-017-0014-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1085059544

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28713588


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