A comprehensive analysis identifies BRAF hotspot mutations associated with gliomas with peculiar epithelial morphology

Ryusuke Hatae, Nobuhiro Hata, Satoshi O. Suzuki, Koji Yoshimoto, Daisuke Kuga, Hideki Murata, Yojiro Akagi, Yuhei Sangatsuda, Toru Iwaki, Masahiro Mizoguchi, Koji Iihara

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Brain tumors harbor various BRAF alterations, the vast majority of which are the BRAF kinase-activating V600E mutation. BRAF mutations are most frequently detected in certain subtypes of low-grade glioma, such as pilocytic astrocytoma (PA), pleomorphic xanthoastrocytoma (PXA), ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNT). However, it is unclear whether gliomas harboring BRAF mutations can be invariably regarded as these glioma subtypes or their derivatives. To address this question, we analyzed 274 gliomas in our institutional case series. We performed high-resolution melting analyses and subsequent direct Sanger sequencing on DNA isolated from snap-frozen tumor tissues. As expected, BRAF mutations were detected in the aforementioned low-grade gliomas: in 4/27 PAs, 2/3 PXAs, 4/8 GGs, and 1/6 DNTs. In addition to these gliomas, 1/2 astroblastomas (ABs) and 2/122 glioblastomas (GBs) harbored BRAF mutations. Pathological investigation of the two GBs revealed that one was a GB displaying epithelial features that presumably arose from a precedent GG, whereas the other GB, which harbored a rare G596 A mutation, showed marked epithelial features, including astroblastic rosettes. Our results indicate that in addition to being present in established BRAF-associated gliomas, BRAF mutations might be associated with epithelial features in high-grade gliomas, including sheet-like arrangement of polygonal tumor cells with a plump cytoplasm and astroblastic rosettes, and thus could potentially serve as a genetic marker for these features.

Original languageEnglish
Pages (from-to)191-199
Number of pages9
JournalNeuropathology
Volume37
Issue number3
DOIs
Publication statusPublished - 2017 Jun

Keywords

  • BRAF
  • G596 A
  • astroblastic rosette
  • glioblastoma
  • glioma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology

Fingerprint Dive into the research topics of 'A comprehensive analysis identifies BRAF hotspot mutations associated with gliomas with peculiar epithelial morphology'. Together they form a unique fingerprint.

  • Cite this

    Hatae, R., Hata, N., Suzuki, S. O., Yoshimoto, K., Kuga, D., Murata, H., Akagi, Y., Sangatsuda, Y., Iwaki, T., Mizoguchi, M., & Iihara, K. (2017). A comprehensive analysis identifies BRAF hotspot mutations associated with gliomas with peculiar epithelial morphology. Neuropathology, 37(3), 191-199. https://doi.org/10.1111/neup.12347