A novel, potentially targetable TMEM106B-BRAF fusion in pleomorphic xanthoastrocytoma

Cold Spring Harb Mol Case Stud. 2017 Mar;3(2):a001396. doi: 10.1101/mcs.a001396.

Abstract

Pleomorphic xanthoastrocytoma (PXA) is a World Health Organization (WHO) Grade II glioma occurring primarily in children and young adults. Most PXAs harbor the known activating mutation BRAF V600E. We report a case of locally recurrent PXA with anaplastic features in a 10-yr-old female. The PXA was negative by immunohistochemical (IHC) staining for BRAF V600E mutation. Whole-exome and transcriptome sequencing of the tumor confirmed the absence of BRAF V600E, but identified copy-number alterations (including loss of the tumor suppressor CDKN2A) and a novel TMEM106B-BRAF fusion. Based on similar BRAF fusion proteins, this novel fusion is predicted to result in activation of BRAF signaling. Demonstration of positive IHC for phospho-ERK1/2 and phospho-MEK1/2 supported this prediction, and implicated MEK inhibitors as a potential therapeutic strategy.

Keywords: neoplasm of the central nervous system.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma / genetics*
  • Brain Neoplasms / genetics
  • Child
  • Female
  • Glioma / genetics
  • Humans
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Whole Exome Sequencing

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf