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

• DOI: 10.1073/pnas.1912858116
• Publication Date: 2019-10-08T00:36:32Z
• Authors: Akash J. Patel; Ying-Wooi Wan; Rami Al-Ouran; Jean-Pierre Revelli; Maria F. Cardenas; Mazen Oneissi; Liu Xi; Ali Jalali; John F. Magnotti; Donna M. Muzny; HarshaVardhan Dod...; Sherly Sebastian; Kent A. Heck; J. Clay Goodman; Shankar P. Gopinath; Zhandong Liu; Ganesh Rao; Sharon E. Plon; Daniel Yoshor; David A. Wheeler; Huda Y. Zoghbi; Tiemo J. Klisch
• Keywords: Adult; Aged, 80 and over; Male; 0303 health sciences; DNA Copy Number Variations; Gene Expression Profiling; Cell Cycle; Kv Channel-Interacting Proteins; Middle Aged; Prognosis; Cell Line; Repressor Proteins; Young Adult; 03 medical and health sciences; Disease Progression; Meningeal Neoplasms; Humans; Female; Neoplasm Recurrence, Local; Meningioma; Aged

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.