New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Cell. 2016 Feb 25;164(5):1060-1072. doi: 10.1016/j.cell.2016.01.015.

Abstract

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Central Nervous System Neoplasms / classification
  • Central Nervous System Neoplasms / diagnosis
  • Central Nervous System Neoplasms / genetics*
  • Central Nervous System Neoplasms / pathology*
  • Child
  • DNA Methylation*
  • Forkhead Transcription Factors / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Sequence Data
  • Neuroectodermal Tumors / classification
  • Neuroectodermal Tumors / diagnosis
  • Neuroectodermal Tumors / genetics*
  • Neuroectodermal Tumors / pathology*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Signal Transduction
  • Trans-Activators
  • Tumor Suppressor Proteins / genetics

Substances

  • BCOR protein, human
  • CIC protein, human
  • FOXR2 protein, human
  • Forkhead Transcription Factors
  • MN1 protein, human
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Trans-Activators
  • Tumor Suppressor Proteins