A novel, potentially targetable TMEM106B-BRAF fusion in pleomorphic xanthoastrocytoma
- Susan J. Hsiao1,
- Matthias A. Karajannis2,
- Daniel Diolaiti3,
- Mahesh M. Mansukhani1,
- Julia Glade Bender4,
- Andrew L. Kung3 and
- James H. Garvin Jr.4
- 1Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10032, USA;
- 2Department of Pediatrics, NYU Langone Medical Center, New York, New York 10016, USA;
- 3Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA;
- 4Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA
- Corresponding author: kunga{at}mskcc.org
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.
- Received August 22, 2016.
- Accepted November 14, 2016.
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