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

• DOI: 10.1101/mcs.a001396
• Publication Date: 2016-12-16T04:47:50Z
• Authors: Susan J. Hsiao; Matthias A. Karaj...; Daniel Diolaiti; Mahesh M. Mansukhani; Julia Glade Bender; Andrew L. Kung; James H. Garvin
• Keywords: Pleomorphic xanthoastrocytoma

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 case of locally recurrent PXA with anaplastic features 10-yr-old female. The was negative by immunohistochemical (IHC) staining for V600E mutation. Whole-exome transcriptome sequencing tumor confirmed absence V600E, but identified copy-number alterations (including loss suppressor CDKN2A ) novel TMEM106B - fusion. Based on similar fusion proteins, this predicted to result activation signaling. Demonstration positive IHC phospho-ERK1/2 phospho-MEK1/2 supported prediction, implicated MEK inhibitors as potential therapeutic strategy.