A novel, potentially targetable TMEM106B-BRAF fusion in pleomorphic xanthoastrocytoma
| Autor: | James Garvin, Julia L. Glade Bender, Matthias A. Karajannis, Andrew L. Kung, Mahesh M. Mansukhani, Susan J. Hsiao, Daniel Diolaiti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proto-Oncogene Proteins B-raf endocrine system diseases Biology Astrocytoma medicine.disease_cause World health law.invention 03 medical and health sciences 0302 clinical medicine law CDKN2A Exome Sequencing medicine Grade II Glioma Humans Child neoplasms neoplasm of the central nervous system Pleomorphic xanthoastrocytoma Mutation Brain Neoplasms General Medicine Glioma medicine.disease Fusion protein digestive system diseases 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Immunohistochemistry Suppressor Female Rapid Cancer Communication |
| Zdroj: | Cold Spring Harbor Molecular Case Studies |
| ISSN: | 2373-2873 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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