NTRK3 kinase fusions in Spitz tumours

被引：119

作者：

Yeh, Iwei ^{[1
,2
,3
]}

Tee, Meng Kian ^{[1
,3
]}

Botton, Thomas ^{[1
,3
]}

Shain, A. Hunter ^{[1
,3
]}

Sparatta, Alyssa J. ^{[1
,3
]}

Gagnon, Alexander ^{[1
,2
,3
]}

Vemula, Swapna S. ^{[1
,2
,3
]}

Garrido, Maria C. ^{[1
,3
]}

Nakamaru, Kenji ^{[4
]}

Isoyama, Takeshi ^{[5
]}

McCalmont, Timothy H. ^{[1
,2
,3
]}

LeBoit, Philip E. ^{[1
,2
,3
]}

Bastian, Boris C. ^{[1
,2
,3
]}

机构：

[1] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA

[3] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[4] Daiichi Sankyo Co Ltd, Translat Res & Clin Pharmacol, Tokyo, Japan

[5] Daiichi Sankyo Co Ltd, Oncol Labs, Tokyo, Japan

来源：

JOURNAL OF PATHOLOGY | 2016年 / 240卷 / 03期

关键词：

NTRK3; fusion; Spitz tumour; melanoma; kinase inhibitor; Spitz naevus; atypical Spitz tumour; spitzoid melanoma; oncogene; genetics; BURROWS-WHEELER TRANSFORM; ETV6-NTRK3 GENE FUSION; CONGENITAL FIBROSARCOMA; SEQUENCING DATA; UVEAL MELANOMA; READ ALIGNMENT; MUTATIONS; CANCER; REARRANGEMENTS; LANDSCAPE;

D O I：

10.1002/path.4775

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 C1 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 (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

引用

页码：282 / 290

页数：9

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