ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research Guidelines

  

Authors:	Marchiò, C.; Scaltriti, M.; Ladanyi, M.; Iafrate, A. J.; Bibeau, F.; Dietel, M.; Hechtman, J. F.; Troiani, T.; López-Rios, F.; Douillard, J. Y.; Andrè, F.; Reis-Filho, J. S.
Title:	ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research
Abstract:	Background: NTRK1, NTRK2 and NTRK3 fusions are present in a plethora of malignancies across different histologies. These fusions represent the most frequent mechanism of oncogenic activation of these receptor tyrosine kinases, and biomarkers for the use of TRK small molecule inhibitors. Given the varying frequency of NTRK1/2/3 fusions, crucial to the administration of NTRK inhibitors is the development of optimal approaches for the detection of human cancers harbouring activating NTRK1/2/3 fusion genes. Materials and methods: Experts from several Institutions were recruited by the European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group (TR and PM WG) to review the available methods for the detection of NTRK gene fusions, their potential applications, and strategies for the implementation of a rational approach for the detection of NTRK1/2/3 fusion genes in human malignancies. A consensus on the most reasonable strategy to adopt when screening for NTRK fusions in oncologic patients was sought, and further reviewed and approved by the ESMO TR and PM WG and the ESMO leadership. Results: The main techniques employed for NTRK fusion gene detection include immunohistochemistry, fluorescence in situ hybridization (FISH), RT-PCR, and both RNA-based and DNA-based next generation sequencing (NGS). Each technique has advantages and limitations, and the choice of assays for screening and final diagnosis should also take into account the resources and clinical context. Conclusion: In tumours where NTRK fusions are highly recurrent, FISH, RT-PCR or RNA-based sequencing panels can be used as confirmatory techniques, whereas in the scenario of testing an unselected population where NTRK1/2/3 fusions are uncommon, either front-line sequencing (preferentially RNA-sequencing) or screening by immunohistochemistry followed by sequencing of positive cases should be pursued. © 2019 The Author(s). Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Keywords:	immunohistochemistry; fluorescence in situ hybridisation; next-generation sequencing; ntrk1; ntrk2; ntrk3
Journal Title:	Annals of Oncology
Volume:	30
Issue:	9
ISSN:	0923-7534
Publisher:	Oxford University Press
Date Published:	2019-09-01
Start Page:	1417
End Page:	1427
Language:	English
DOI:	10.1093/annonc/mdz204
PUBMED:	31268127
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85072662511&doi=10.1093%2fannonc%2fmdz204&partnerID=40&md5=9283cbacfa3b71749a0a90de3e4c2f89
Notes:	Article -- Export Date: 1 November 2019 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/155228