Genomic Molecular Classification of CNS Malignancies

Adv Anat Pathol. 2020 Jan;27(1):44-50. doi: 10.1097/PAP.0000000000000254.


Molecular studies have identified distinct genomic drivers providing insights in biology of brain tumors. Advances in genetic and epigenetic analysis, as well as development of mutation-specific antibodies enable more accurate classification of histologically indistinguishable tumors. Compared with histopathologic grading, molecular biomarkers are also superior in predicting natural behavior of tumors and therapeutic response. Diffuse gliomas can be separated in astrocytoma and oligodendroglioma based on IDH1/2, ATRX, and TP53 mutational status. Pediatric gliomas are molecularly distinct from adult tumors and molecular drivers include histone H3 genes and fusions involving the MAPK pathway. Using genetic and epigenetic profiling, ependymal tumors, medulloblastomas, and atypical teratoid/rhabdoid tumors can be separated in biologically and clinically distinct entities. Identification of novel gene fusions and matched DNA methylation signatures enable accurate diagnosis of primitive neuroectodermal tumors, which were previously misdiagnosed. Genomic classification of central nervous system tumors is being readily translated into the clinical practice and will enable molecularly based patient management and clinical trials.

Publication types

  • Review

MeSH terms

  • Brain / pathology
  • Central Nervous System Neoplasms / genetics*
  • Central Nervous System Neoplasms / pathology
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Neoplasms, Germ Cell and Embryonal / pathology