Detection of H3K27M mutation in cases of brain stem subependymoma

Hum Pathol. 2019 Feb:84:262-269. doi: 10.1016/j.humpath.2018.10.011. Epub 2018 Oct 30.

Abstract

Subependymomas are rare, slow-growing, grade I glial tumors of the central nervous system. Recently, diffuse midline gliomas with mutations in the H3.1 or H3.3 genes at the position of amino acid 27, resulting in the replacement of lysine by methionine (K27M), were defined as the new grade IV entity. As H3K27M mutations have been reported in midline gliomas, gangliogliomas, and pilocytic astrocytomas, whether they occur in midline subependymomas has been unclear. We determined whether any such mutations can be found in them and analyzed the prognostic relevance of any such mutations in subependymomas. Four subependymomas, all in the brain stem, harbored H3K27M mutations. No such mutation was found in any of the subependymomas from other locations. The mutations were identified by immunohistochemical stains and confirmed with Sanger sequencing. The median follow-up of the patients with the mutations in their tumors was 3.2 years, and 3 are still alive, having received no adjuvant therapy. We demonstrate that H3K27M mutation can occur in brainstem subependymomas; despite the presence of H3K27M mutation, these cases should not be diagnosed or treated as grade IV tumors because they showed a better outcome than the outcome of diffuse midline H3K27M mutant glioma. Our conclusion is not only that brainstem subependymomas can have H3K27M mutations but that they do not carry the rapidly lethal prognosis with which these mutations are usually associated because of their discovery in diffuse intrinsic pontine gliomas.

Keywords: Brain stem neoplasm; H3K27M mutation; Sanger sequencing; Subependymoma.

MeSH terms

  • Adolescent
  • Adult
  • Brain Stem Neoplasms / genetics
  • Brain Stem Neoplasms / pathology*
  • Female
  • Glioma, Subependymal / genetics*
  • Glioma, Subependymal / pathology*
  • Histones / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Young Adult

Substances

  • Histones