NTRK3 kinase fusions in Spitz tumours

Iwei Yeh; Meng Kian Tee; Thomas Botton; A Hunter Shain; Alyssa J Sparatta; Alexander Gagnon; Swapna S Vemula; Maria C Garrido; Kenji Nakamaru; Takeshi Isoyama; Timothy H McCalmont; Philip E LeBoit; Boris C Bastian

doi:10.1002/path.4775

journal article Oct 19, 2016

NTRK3 kinase fusions in Spitz tumours

Meng Kian Tee Thomas Botton A Hunter Shain Alyssa J Sparatta Alexander Gagnon Swapna S Vemula Maria C Garrido Kenji Nakamaru Takeshi Isoyama Timothy H McCalmont Philip E LeBoit Boris C Bastian

The Journal of Pathology Vol. 240 No. 3 pp. 282-290 · Wiley

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Abstract

AbstractOncogenic 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.

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Metrics

146

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46

References

Details

Published: Oct 19, 2016
Vol/Issue: 240(3)
Pages: 282-290
License: View

Authors

I

Iwei Yeh

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

M

Meng Kian Tee

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

T

Thomas Botton

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

A

A Hunter Shain

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

A

Alyssa J Sparatta

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

A

Alexander Gagnon

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

S

Swapna S Vemula

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

M

Maria C Garrido

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

K

Kenji Nakamaru

Translational Research and Clinical Pharmacology Daiichi Sankyo, Co., Ltd Tokyo Japan

T

Takeshi Isoyama

Oncology Laboratories Daiichi Sankyo, Co., Ltd Tokyo Japan

T

Timothy H McCalmont

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

P

Philip E LeBoit

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

B

Boris C Bastian

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

Funding

National Institutes of Health Award: P01 CA025874

Melanoma Research Alliance

Dermatology Foundation

Daiichi-Sankyo

Melanoma Research Foundation

Cite This Article

Iwei Yeh, Meng Kian Tee, Thomas Botton, et al. (2016). NTRK3 kinase fusions in Spitz tumours. The Journal of Pathology, 240(3), 282-290. https://doi.org/10.1002/path.4775

NTRK3 kinase fusions in Spitz tumours

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