NTRK3 Kinase Fusions in Spitz Tumours

Overview

Journal J Pathol

Specialty Pathology

Date 2016 Aug 2

PMID 27477320

Citations 54

Authors

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

Affiliations

Soon will be listed here.

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.

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References

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

Yeh I, Botton T, Talevich E, Shain A, Sparatta A, De la Fouchardiere A . Activating MET kinase rearrangements in melanoma and Spitz tumours. Nat Commun. 2015; 6:7174. PMC: 4446791. DOI: 10.1038/ncomms8174. View

Van Raamsdonk C, Bezrookove V, Green G, Bauer J, Gaugler L, OBrien J . Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2008; 457(7229):599-602. PMC: 2696133. DOI: 10.1038/nature07586. View

Bennett D, Cooper P, Hart I . A line of non-tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumour promoter for growth. Int J Cancer. 1987; 39(3):414-8. DOI: 10.1002/ijc.2910390324. View

Davies H, Bignell G, Cox C, Stephens P, Edkins S, Clegg S . Mutations of the BRAF gene in human cancer. Nature. 2002; 417(6892):949-54. DOI: 10.1038/nature00766. View

Leeman-Neill R, Kelly L, Liu P, Brenner A, Little M, Bogdanova T . ETV6-NTRK3 is a common chromosomal rearrangement in radiation-associated thyroid cancer. Cancer. 2013; 120(6):799-807. PMC: 3947712. DOI: 10.1002/cncr.28484. View

Huang E, Reichardt L . Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem. 2003; 72:609-42. DOI: 10.1146/annurev.biochem.72.121801.161629. View

Botton T, Yeh I, Nelson T, Vemula S, Sparatta A, Garrido M . Recurrent BRAF kinase fusions in melanocytic tumors offer an opportunity for targeted therapy. Pigment Cell Melanoma Res. 2013; 26(6):845-51. PMC: 3808507. DOI: 10.1111/pcmr.12148. View

Stransky N, Cerami E, Schalm S, Kim J, Lengauer C . The landscape of kinase fusions in cancer. Nat Commun. 2014; 5:4846. PMC: 4175590. DOI: 10.1038/ncomms5846. View

10.

Hodis E, Watson I, Kryukov G, Arold S, Imielinski M, Theurillat J . A landscape of driver mutations in melanoma. Cell. 2012; 150(2):251-63. PMC: 3600117. DOI: 10.1016/j.cell.2012.06.024. View

11.

Hutchinson K, Lipson D, Stephens P, Otto G, Lehmann B, Lyle P . BRAF fusions define a distinct molecular subset of melanomas with potential sensitivity to MEK inhibition. Clin Cancer Res. 2013; 19(24):6696-702. PMC: 3880773. DOI: 10.1158/1078-0432.CCR-13-1746. View

12.

Brenca M, Rossi S, Polano M, Gasparotto D, Zanatta L, Racanelli D . Transcriptome sequencing identifies ETV6-NTRK3 as a gene fusion involved in GIST. J Pathol. 2015; 238(4):543-9. DOI: 10.1002/path.4677. View

13.

Tognon C, Mackereth C, Somasiri A, McIntosh L, Sorensen P . Mutations in the SAM domain of the ETV6-NTRK3 chimeric tyrosine kinase block polymerization and transformation activity. Mol Cell Biol. 2004; 24(11):4636-50. PMC: 416412. DOI: 10.1128/MCB.24.11.4636-4650.2004. View

14.

Knezevich S, Garnett M, Pysher T, Beckwith J, Grundy P, Sorensen P . ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res. 1998; 58(22):5046-8. View

15.

Wiesner T, He J, Yelensky R, Esteve-Puig R, Botton T, Yeh I . Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat Commun. 2014; 5:3116. PMC: 4084638. DOI: 10.1038/ncomms4116. View

16.

Van Raamsdonk C, Griewank K, Crosby M, Garrido M, Vemula S, Wiesner T . Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010; 363(23):2191-9. PMC: 3107972. DOI: 10.1056/NEJMoa1000584. View

17.

Wang J, Mullighan C, Easton J, Roberts S, Heatley S, Ma J . CREST maps somatic structural variation in cancer genomes with base-pair resolution. Nat Methods. 2011; 8(8):652-4. PMC: 3527068. DOI: 10.1038/nmeth.1628. View

18.

Taipale M, Krykbaeva I, Whitesell L, Santagata S, Zhang J, Liu Q . Chaperones as thermodynamic sensors of drug-target interactions reveal kinase inhibitor specificities in living cells. Nat Biotechnol. 2013; 31(7):630-7. PMC: 3774174. DOI: 10.1038/nbt.2620. View

19.

Wu G, Diaz A, Paugh B, Rankin S, Ju B, Li Y . The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet. 2014; 46(5):444-450. PMC: 4056452. DOI: 10.1038/ng.2938. View

20.

Nissan M, Pratilas C, Jones A, Ramirez R, Won H, Liu C . Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence. Cancer Res. 2014; 74(8):2340-50. PMC: 4005042. DOI: 10.1158/0008-5472.CAN-13-2625. View