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

Abstract 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...

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Autores principales:	Christopher Alvarez-Breckenridge, Julie J. Miller, Naema Nayyar, Corey M. Gill, Andrew Kaneb, Megan D’Andrea, Long P. Le, Jesse Lee, Ju Cheng, Zongli Zheng, William E. Butler, Pratik Multani, Edna Chow Maneval, Sun Ha Paek, Brian D. Toyota, Dora Dias-Santagata, Sandro Santagata, Javier Romero, Alice T. Shaw, Anna F. Farago, Stephen Yip, Daniel P. Cahill, Tracy T. Batchelor, A. John Iafrate, Priscilla K. Brastianos
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/566d486d09384fbf8d3ccde6c3b6828b
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spelling	oai:doaj.org-article:566d486d09384fbf8d3ccde6c3b6828b2021-12-02T16:05:43ZClinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor10.1038/s41698-017-0009-y2397-768Xhttps://doaj.org/article/566d486d09384fbf8d3ccde6c3b6828b2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41698-017-0009-yhttps://doaj.org/toc/2397-768XAbstract 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.Christopher Alvarez-BreckenridgeJulie J. MillerNaema NayyarCorey M. GillAndrew KanebMegan D’AndreaLong P. LeJesse LeeJu ChengZongli ZhengWilliam E. ButlerPratik MultaniEdna Chow ManevalSun Ha PaekBrian D. ToyotaDora Dias-SantagataSandro SantagataJavier RomeroAlice T. ShawAnna F. FaragoStephen YipDaniel P. CahillTracy T. BatchelorA. John IafratePriscilla K. BrastianosNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 1, Iss 1, Pp 1-5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Christopher Alvarez-Breckenridge Julie J. Miller Naema Nayyar Corey M. Gill Andrew Kaneb Megan D’Andrea Long P. Le Jesse Lee Ju Cheng Zongli Zheng William E. Butler Pratik Multani Edna Chow Maneval Sun Ha Paek Brian D. Toyota Dora Dias-Santagata Sandro Santagata Javier Romero Alice T. Shaw Anna F. Farago Stephen Yip Daniel P. Cahill Tracy T. Batchelor A. John Iafrate Priscilla K. Brastianos Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor
description	Abstract 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.
format	article
author	Christopher Alvarez-Breckenridge Julie J. Miller Naema Nayyar Corey M. Gill Andrew Kaneb Megan D’Andrea Long P. Le Jesse Lee Ju Cheng Zongli Zheng William E. Butler Pratik Multani Edna Chow Maneval Sun Ha Paek Brian D. Toyota Dora Dias-Santagata Sandro Santagata Javier Romero Alice T. Shaw Anna F. Farago Stephen Yip Daniel P. Cahill Tracy T. Batchelor A. John Iafrate Priscilla K. Brastianos
author_facet	Christopher Alvarez-Breckenridge Julie J. Miller Naema Nayyar Corey M. Gill Andrew Kaneb Megan D’Andrea Long P. Le Jesse Lee Ju Cheng Zongli Zheng William E. Butler Pratik Multani Edna Chow Maneval Sun Ha Paek Brian D. Toyota Dora Dias-Santagata Sandro Santagata Javier Romero Alice T. Shaw Anna F. Farago Stephen Yip Daniel P. Cahill Tracy T. Batchelor A. John Iafrate Priscilla K. Brastianos
author_sort	Christopher Alvarez-Breckenridge
title	Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor
title_short	Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor
title_full	Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor
title_fullStr	Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor
title_full_unstemmed	Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor
title_sort	clinical and radiographic response following targeting of bcan-ntrk1 fusion in glioneuronal tumor
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/566d486d09384fbf8d3ccde6c3b6828b
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Clinical and radiographic response following targeting of BCAN-NTRK1 fusion in glioneuronal tumor

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