Cerebellar high-grade gliomas do not present the same molecular alterations as supratentorial high-grade gliomas and may show histone H3 gene mutations

Clin Neuropathol. 2018 Sep/Oct;37(5):209-216. doi: 10.5414/NP301104.

Abstract

Numerous molecular alterations have been described in supratentorial high-grade gliomas (1p19q co-deletion, IDH1/2, histone H3, hTERT promotor mutations, loss of ATRX) which have led to a new histomolecular classification of diffuse gliomas. We aimed at describing these alterations in a series of 19 adults with pure cerebellar high-grade gliomas. Systematic immunohistochemical analyses, including that of IDH1R132H, ATRX, p53, PTEN, EGFR, p16, FGFR3, BRAFV600E, mismatch repair proteins, H3K27me3, H3K36me3, and H3K27M; molecular analyses of IDH1/2, hTERT, BRAF, H3F3A, and HIST1H3B mutation hotspots; and EGFR, PTEN FISH were retrospectively performed in a multicentric study. We histopathologically identified 14 glioblastomas, 4 grade III astrocytomas and 1 gliosarcoma. Two cases showed a H3F3A K27M mutation. Only one case harbored a classical profile of glioblastoma with hTERT mutation, EGFR gain and 10q loss. The most frequent alteration was the absence of p16 immunoexpression. We report a histomolecular analysis of pure cerebellar high grade gliomas. The histomolecular profile appears to be different from that of supratentorial gliomas, with no IDH1/2 gene mutations and only 1 case with a classic profile of de novo glioblastoma. In 2 cases, we identified H3F3A K27M mutation, classically described in pediatric midline gliomas. .

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cerebellar Neoplasms / genetics*
  • Cerebellar Neoplasms / pathology*
  • Female
  • Gene Expression Profiling
  • Glioma / genetics*
  • Glioma / pathology*
  • Histones / genetics*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Proteins / genetics
  • Retrospective Studies
  • Supratentorial Neoplasms / genetics*
  • Supratentorial Neoplasms / pathology*
  • Young Adult

Substances

  • Histones
  • Neoplasm Proteins