Spinal Pleomorphic Xanthoastrocytoma With a QKI-RAF1 Fusion

Elena V. Daoud, Megan Wachsmann, Timothy E. Richardson, Divya Mella, Edward Pan, Anna Schwarzbach, Dwight Oliver, Kimmo J Hatanpaa

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Pleomorphic xanthoastrocytoma (PXA) is a slow-growing neoplasm that predominantly affects the pediatric and young adult population. This neoplasm has a good prognosis, with a median 10-year survival rate of 70%. The majority of tumors are supratentorial and arise in the temporal lobe, while spinal tumors are extremely rare, with only 8 reported cases. Molecular perturbations involving the MAPK/ERK signaling pathway have been described in PXAs. The most common mutation is BRAF V600E in 60%-80% of cases. Other mechanisms activating this pathway in the absence of this mutation are rare and include CRAF (RAF1) fusion genes. We report a PXA case in the cervical spinal cord of a 49-year-old man with slowly progressive coordination difficulties and extremity numbness. The tumor was negative for the V600E mutation, but 2 RNA sequencing platforms detected a QKI-RAF1 fusion (t(6; 3)(q26; p25)), which has not been previously reported in PXAs. This fusion is known to activate MAPK/ERK and PI3K/mTOR signaling. Although first- and second-generation RAF inhibitors are predicted to be ineffective, this fusion may be targetable by the novel RAF inhibitor LY3009120 and to some extent by the MEK inhibitor trametinib. Genetic analysis to screen for MAPK/ERK pathway mutations is warranted on PXAs negative for the V600E mutation.

Original languageEnglish (US)
Pages (from-to)10-14
Number of pages5
JournalJournal of Neuropathology and Experimental Neurology
Volume78
Issue number1
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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