Comprehensive genomic profiling identifies novel NTRK fusions in neuroendocrine tumors

// Darren S. Sigal 1 , Munveer S. Bhangoo 1 , Jonathan A. Hermel 2 , Dean C. Pavlick 3 , Garrett Frampton 3 , Vincent A. Miller 3 , Jeffrey S. Ross 3 and Siraj M. Ali 3 1 Division of Hematology/Oncology, Scripps Clinic Medical Group, La Jolla, CA, USA 2 Department of Graduate Medical Education, Tulane University School of Medicine, New Orleans, LA, USA 3 Foundation Medicine, Inc. Cambridge, MA, USA Correspondence to: Darren S. Sigal, email: Sigal.darren@scrippshealth.org Keywords: next-generation sequencing; neuroendocrine tumor; NET; NTRK; neuroendocrine cancer Received: August 10, 2018      Accepted: October 06, 2018      Published: November 09, 2018 ABSTRACT CGP results from >60,000 cases were screened to identify NTRK fusion events from cases of neuroendocrine tumors. 2417 NET patients from diverse anatomic sites were identified. From this dataset, six cases harbored NTRK fusions which included intra- and inter-chromosomal translocations. A NTRK fusion frequency of approximately 0.3% was found across all subtypes of NETs. Three cases involved translocations of NTRK1 with unique fusion partners (GPATCH4, PIP5K1A, CCDC19). Co-occurring alterations occurred in five cases. NTRK alterations were identified in nearly the full spectrum of NETs, including from the small intestine, pancreas, lung, and others. With the late stage clinical development of NTRK TKIs (including entrectinib and larotrectinib), these findings may further inform targeted approaches to therapy in NET.