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J Pathol. 2016 Nov;240(3):282-290. doi: 10.1002/path.4775.

NTRK3 kinase fusions in Spitz tumours.

Author information

1
Department of Dermatology, University of California San Francisco, San Francisco, CA, USA. iwei.yeh@ucsf.edu.
2
Department of Pathology, University of California San Francisco, San Francisco, CA, USA. iwei.yeh@ucsf.edu.
3
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. iwei.yeh@ucsf.edu.
4
Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
5
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
6
Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
7
Translational Research and Clinical Pharmacology, Daiichi Sankyo, Co., Ltd, Tokyo, Japan.
8
Oncology Laboratories, Daiichi Sankyo, Co., Ltd, Tokyo, Japan.
9
Department of Dermatology, University of California San Francisco, San Francisco, CA, USA. boris.bastian@ucsf.edu.
10
Department of Pathology, University of California San Francisco, San Francisco, CA, USA. boris.bastian@ucsf.edu.
11
Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. boris.bastian@ucsf.edu.

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.

KEYWORDS:

NTRK3 fusion; Spitz naevus; Spitz tumour; atypical Spitz tumour; genetics; kinase inhibitor; melanoma; oncogene; spitzoid melanoma

PMID:
27477320
PMCID:
PMC5071153
DOI:
10.1002/path.4775
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

K.N. and T.I. are employees of Daiichi Sankyo, Co., Ltd. The remaining authors declare no conflict of interest.

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