Genetic Alterations in Gliosarcoma and Giant Cell Glioblastoma

Ji Eun Oh, Takashi Ohta, Naosuke Nonoguchi, Kaishi Satomi, David Capper, Daniela Pierscianek, Ulrich Sure, Anne Vital, Werner Paulus, Michel Mittelbronn, Manila Antonelli, Paul Kleihues, Felice Giangaspero, Hiroko Ohgaki*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

47 Citations (Scopus)

Abstract

The majority of glioblastomas develop rapidly with a short clinical history (primary glioblastoma IDH wild-type), whereas secondary glioblastomas progress from diffuse astrocytoma or anaplastic astrocytoma. IDH mutations are the genetic hallmark of secondary glioblastomas. Gliosarcomas and giant cell glioblastomas are rare histological glioblastoma variants, which usually develop rapidly. We determined the genetic patterns of 36 gliosarcomas and 19 giant cell glioblastomas. IDH1 and IDH2 mutations were absent in all 36 gliosarcomas and in 18 of 19 giant cell glioblastomas analyzed, indicating that they are histological variants of primary glioblastoma. Furthermore, LOH 10q (88%) and TERT promoter mutations (83%) were frequent in gliosarcomas. Copy number profiling using the 450k methylome array in 5 gliosarcomas revealed CDKN2A homozygous deletion (3 cases), trisomy chromosome 7 (2 cases), and monosomy chromosome 10 (2 cases). Giant cell glioblastomas had LOH 10q in 50% and LOH 19q in 42% of cases. ATRX loss was detected immunohistochemically in 19% of giant cell glioblastomas, but absent in 17 gliosarcomas. These and previous results suggest that gliosarcomas are a variant of, and genetically similar to, primary glioblastomas, except for a lack of EGFR amplification, while giant cell glioblastoma occupies a hybrid position between primary and secondary glioblastomas.

Original languageEnglish
Pages (from-to)517-522
Number of pages6
JournalBrain Pathology
Volume26
Issue number4
DOIs
Publication statusPublished - 1 Jul 2016
Externally publishedYes

Keywords

  • 10q
  • 19q
  • IDH mutation
  • TERT mutation
  • giant cell glioblastoma
  • gliosarcoma

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