Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors.

 
TitleMolecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors.
Publication TypeJournal Article
Year of Publication2019
AuthorsPatel, AJ, Wan, Y-W, Al-Ouran, R, Revelli, J-P, Cardenas, MF, Oneissi, M, Xi, L, Jalali, A, Magnotti, JF, Muzny, DM, Doddapaneni, H, Sebastian, S, Heck, KA, J Goodman, C, Gopinath, SP, Liu, Z, Rao, G, Plon, SE, Yoshor, D, Wheeler, DA, Zoghbi, HY, Klisch, TJ
JournalProc Natl Acad Sci U S A
Volume116
Issue43
Pagination21715-21726
Date Published2019 Oct 22
ISSN1091-6490
Abstract

Meningiomas account for one-third of all primary brain tumors. Although typically benign, about 20% of meningiomas are aggressive, and despite the rigor of the current histopathological classification system there remains considerable uncertainty in predicting tumor behavior. Here, we analyzed 160 tumors from all 3 World Health Organization (WHO) grades (I through III) using clinical, gene expression, and sequencing data. Unsupervised clustering analysis identified 3 molecular types (A, B, and C) that reliably predicted recurrence. These groups did not directly correlate with the WHO grading system, which classifies more than half of the tumors in the most aggressive molecular type as benign. Transcriptional and biochemical analyses revealed that aggressive meningiomas involve loss of the repressor function of the DREAM complex, which results in cell-cycle activation; only tumors in this category tend to recur after full resection. These findings should improve our ability to predict recurrence and develop targeted treatments for these clinically challenging tumors.

DOI10.1073/pnas.1912858116
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID31591222
PubMed Central IDPMC6815170
Grant ListK08 NS102474 / NS / NINDS NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States