title: NTRK3 kinase fusions in Spitz tumours.
abstract: Oncogenic fusions in TRK family receptor tyrosine kinases have been identified in several cancers and can serve as therapeutic targets. We identified ETV6-NTRK3, MYO5A-NTRK3 and MYH9-NTRK3 fusions in Spitz tumours, and demonstrated that NTRK3 fusions constitutively activate the mitogen-activated protein kinase, phosphoinositide 3-kinase and phospholipase Cγ1 pathways in melanocytes. This signalling was inhibited by DS-6051a, a small-molecule inhibitor of NTRK1/2/3 and ROS1. NTRK3 fusions expand the range of oncogenic kinase fusions in melanocytic neoplasms and offer targets for a small subset of melanomas for which no targeted options currently exist. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA. iwei.yeh@ucsf.edu.|Department of Pathology, University of California San Francisco, San Francisco, CA, USA. iwei.yeh@ucsf.edu.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. iwei.yeh@ucsf.edu.
authors.forename: Iwei
authors.initials: I
authors.lastname: Yeh
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Meng Kian
authors.initials: MK
authors.lastname: Tee
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Botton
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: A Hunter
authors.initials: AH
authors.lastname: Shain
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Alyssa J
authors.initials: AJ
authors.lastname: Sparatta
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.|Department of Pathology, University of California San Francisco, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gagnon
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.|Department of Pathology, University of California San Francisco, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Swapna S
authors.initials: SS
authors.lastname: Vemula
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Garrido
authors.affiliation: Translational Research and Clinical Pharmacology, Daiichi Sankyo, Co., Ltd, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakamaru
authors.affiliation: Oncology Laboratories, Daiichi Sankyo, Co., Ltd, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Isoyama
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.|Department of Pathology, University of California San Francisco, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: McCalmont
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.|Department of Pathology, University of California San Francisco, San Francisco, CA, USA.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Philip E
authors.initials: PE
authors.lastname: LeBoit
authors.affiliation: Department of Dermatology, University of California San Francisco, San Francisco, CA, USA. boris.bastian@ucsf.edu.|Department of Pathology, University of California San Francisco, San Francisco, CA, USA. boris.bastian@ucsf.edu.|Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. boris.bastian@ucsf.edu.
authors.forename: Boris C
authors.initials: BC
authors.lastname: Bastian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D000070820:Discoidin Domain Receptor 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000235:genetics* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D024701:Myosin Type V / Q000235:genetics* / Q000378:metabolism; D018332:Nevus, Epithelioid and Spindle Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D050596:Oncogene Fusion; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D012878:Skin Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D000070820:Discoidin Domain Receptor 2; D020928:Mitogen-Activated Protein Kinases; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains; D024701:Myosin Type V; D019869:Phosphatidylinositol 3-Kinases; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C103814:MYH9 protein, human; C077511:MYO5A protein, human; C000603239:DDR2 protein, human
keywords: NTRK3 fusion; Spitz naevus; Spitz tumour; atypical Spitz tumour; genetics; kinase inhibitor; melanoma; oncogene; spitzoid melanoma