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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 C?1 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.

SUBMITTER: Yeh I

PROVIDER: S-EPMC5071153 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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NTRK3 kinase fusions in Spitz tumours.

Yeh Iwei I Tee Meng Kian MK Botton Thomas T Shain A Hunter AH Sparatta Alyssa J AJ Gagnon Alexander A Vemula Swapna S SS Garrido Maria C MC Nakamaru Kenji K Isoyama Takeshi T McCalmont Timothy H TH LeBoit Philip E PE Bastian Boris C BC

The Journal of pathology 20161101 3

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 ...[more]

PMID: 27477320

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Kinase fusions are frequent in Spitz tumours and spitzoid melanomas.

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NTRK3 kinase fusions in melanocytic tumors

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