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Cheng, Ju

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Cheng, Ju

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    Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor
    (Nature Publishing Group UK, 2017) Alvarez-Breckenridge, Christopher; Miller, Julie; Nayyar, Naema; Gill, Corey M.; Kaneb, Andrew; D’Andrea, Megan; Le, Long P.; Lee, Jesse; Cheng, Ju; Zheng, Zongli; Butler, William; Multani, Pratik; Chow Maneval, Edna; Ha Paek, Sun; Toyota, Brian D.; Dias-Santagata, Dora; Santagata, Sandro; Romero, Javier; Shaw, Alice; Farago, Anna; Yip, Stephen; Cahill, Daniel; Batchelor, Tracy; Iafrate, A. John; Brastianos, Priscilla
    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.