Multiplatform Molecular Profiling Reveals Epigenomic Intratumor Heterogeneity in Ependymoma

Cell Rep. 2020 Feb 4;30(5):1300-1309.e5. doi: 10.1016/j.celrep.2020.01.018.


Ependymomas exist within distinct genetic subgroups, but the molecular diversity within individual ependymomas is unknown. We perform multiplatform molecular profiling of 6 spatially distinct samples from an ependymoma with C11orf95-RELA fusion. DNA methylation and RNA sequencing distinguish clusters of samples according to neuronal development gene expression programs that could also be delineated by differences in magnetic resonance blood perfusion. Exome sequencing and phylogenetic analysis reveal epigenomic intratumor heterogeneity and suggest that chromosomal structural alterations may precede accumulation of single-nucleotide variants during ependymoma tumorigenesis. In sum, these findings shed light on the oncogenesis and intratumor heterogeneity of ependymoma.

Keywords: C11orf95-RELA; DNA methylation; RNA sequencing; SETD2; brain tumor; cancer; ependymoma; epigenomics; exome sequencing; magnetic resonance imaging.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Chromosome Aberrations
  • Ependymoma / diagnostic imaging
  • Ependymoma / genetics*
  • Epigenomics*
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Genetic Heterogeneity*
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism
  • Humans
  • Male
  • Mutation / genetics
  • Neurons / pathology
  • Phylogeny
  • Proteins / metabolism
  • Transcription Factor RelA / metabolism


  • C11orf95 protein, human
  • Proteins
  • Transcription Factor RelA
  • Histone-Lysine N-Methyltransferase
  • SETD2 protein, human

Supplementary concepts

  • Familial ependymoma