Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups

Cancer Cell. 2015 May 11;27(5):728-43. doi: 10.1016/j.ccell.2015.04.002.

Abstract

Ependymal tumors across age groups are currently classified and graded solely by histopathology. It is, however, commonly accepted that this classification scheme has limited clinical utility based on its lack of reproducibility in predicting patients' outcome. We aimed at establishing a uniform molecular classification using DNA methylation profiling. Nine molecular subgroups were identified in a large cohort of 500 tumors, 3 in each anatomical compartment of the CNS, spine, posterior fossa, supratentorial. Two supratentorial subgroups are characterized by prototypic fusion genes involving RELA and YAP1, respectively. Regarding clinical associations, the molecular classification proposed herein outperforms the current histopathological classification and thus might serve as a basis for the next World Health Organization classification of CNS tumors.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adolescent
  • Adult
  • Age Factors*
  • Aged
  • Central Nervous System Neoplasms / classification
  • Central Nervous System Neoplasms / genetics
  • Central Nervous System Neoplasms / pathology*
  • Child
  • Child, Preschool
  • DNA Methylation
  • Ependymoma / classification
  • Ependymoma / genetics
  • Ependymoma / pathology*
  • Female
  • Gene Dosage
  • Gene Expression Profiling
  • Gene Fusion
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Phosphoproteins / genetics
  • Transcription Factors
  • Transcription, Genetic
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • Transcription Factors
  • YAP1 (Yes-associated) protein, human

Associated data

  • GEO/GSE64415
  • GEO/GSE65362