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

Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21715-21726. doi: 10.1073/pnas.1912858116. Epub 2019 Oct 7.


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.

Keywords: NF2; PRC2; brain tumor; classification; oncogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Line
  • DNA Copy Number Variations / genetics
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Humans
  • Kv Channel-Interacting Proteins / genetics*
  • Male
  • Meningeal Neoplasms / genetics*
  • Meningeal Neoplasms / pathology
  • Meningioma / genetics*
  • Meningioma / pathology
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Prognosis
  • Repressor Proteins / genetics*
  • Young Adult


  • KCNIP3 protein, human
  • Kv Channel-Interacting Proteins
  • Repressor Proteins