Glioneuronal tumors constitute a histologically diverse group of primary central nervous system neoplasms that are typically slow-growing and managed conservatively.  Genetic alterations associated with glioneuronal tumors include BRAF mutations and oncogenic fusions.  To further characterize this group of tumors, we collected a cohort of 26 glioneuronal tumors and performed in-depth genomic analysis.  We identified mutations in BRAF (34%) and oncogenic fusions (30%), consistent with previously published reports.  In addition, we discovered novel oncogenic fusions involving members of the NTRK gene family in a subset of our cohort.  One-patient with BCAN exon 13 fused to NTRK1 exon 11 initially underwent a subtotal resection for a 4th ventricular glioneuronal tumor but ultimately required additional therapy due to progressive, symptomatic disease.  Given the patient’s targetable fusion, the patient was enrolled on a clinical trial with entrectinib, a pan-Trk, ROS1, and ALK (anaplastic lymphoma kinase) inhibitor.  The patient was treated for 11 months and during this time volumetric analysis of the lesion demonstrated a maximum reduction of 60% in the contrast-enhancing tumor compared to his pre-treatment magnetic resonance imaging study.  The radiologic response was associated with resolution of his clinical symptoms and was maintained for 11 months on treatment.  This report of a BCAN-NTRK1 fusion in glioneuronal tumors highlights its clinical importance as a novel, targetable alteration. 

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en_US

en

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Nature Publishing Group UK

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doi:10.1038/s41698-017-0009-y

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871889/pdf/

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LAA

en_US

dc.title

Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor