PMID- 31268127 OWN - NLM STAT- MEDLINE DCOM- 20200603 LR - 20240229 IS - 1569-8041 (Electronic) IS - 0923-7534 (Linking) VI - 30 IP - 9 DP - 2019 Sep 1 TI - ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. PG - 1417-1427 LID - S0923-7534(19)45992-9 [pii] LID - 10.1093/annonc/mdz204 [doi] AB - 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. CI - (c) The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Marchio, C AU - Marchio C AD - Department of Medical Sciences, University of Turin, Turin; Division of Pathology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy. FAU - Scaltriti, M AU - Scaltriti M AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York; Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York. FAU - Ladanyi, M AU - Ladanyi M AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York. FAU - Iafrate, A J AU - Iafrate AJ AD - Department of Pathology, Massachusetts General Hospital, Boston; Department of Pathology, Harvard Medical School, Boston, USA. FAU - Bibeau, F AU - Bibeau F AD - Department of Pathology, Caen University Hospital, Caen, France. FAU - Dietel, M AU - Dietel M AD - Institute of Pathology, Charite, University Medicine Berlin, Berlin, Germany. FAU - Hechtman, J F AU - Hechtman JF AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York. FAU - Troiani, T AU - Troiani T AD - Medical Oncology, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Lopez-Rios, F AU - Lopez-Rios F AD - Pathology & Targeted Therapies Laboratory, HM Sanchinarro University Hospital, Madrid, Spain. FAU - Douillard, J-Y AU - Douillard JY AD - European Society for Medical Oncology, Lugano, Switzerland. FAU - Andre, F AU - Andre F AD - Department of Medical Oncology, INSERM Unit 981, Institut Gustave Roussy, Villejuif, France. Electronic address: education@esmo.org. FAU - Reis-Filho, J S AU - Reis-Filho JS AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0 (Biomarkers, Tumor) RN - 0 (Membrane Glycoproteins) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (Receptor, trkC) RN - EC 2.7.10.1 (tropomyosin-related kinase-B, human) SB - IM MH - Biomarkers, Tumor/genetics/isolation & purification MH - High-Throughput Nucleotide Sequencing MH - Humans MH - Immunohistochemistry/standards MH - In Situ Hybridization, Fluorescence/standards MH - Medical Oncology/standards MH - Membrane Glycoproteins/genetics/*isolation & purification MH - Neoplasms/*diagnosis/drug therapy/genetics MH - Oncogene Proteins, Fusion/genetics/*isolation & purification MH - Precision Medicine/standards MH - Protein Kinase Inhibitors/therapeutic use MH - Receptor, trkA/genetics/*isolation & purification MH - Receptor, trkB/genetics/*isolation & purification MH - Receptor, trkC/genetics/*isolation & purification MH - Translational Research, Biomedical/standards OTO - NOTNLM OT - NTRK1 OT - NTRK2 OT - NTRK3 OT - fluorescence in situ hybridisation OT - immunohistochemistry OT - next-generation sequencing EDAT- 2019/07/04 06:00 MHDA- 2020/06/04 06:00 CRDT- 2019/07/04 06:00 PHST- 2019/07/04 06:00 [pubmed] PHST- 2020/06/04 06:00 [medline] PHST- 2019/07/04 06:00 [entrez] AID - S0923-7534(19)45992-9 [pii] AID - 10.1093/annonc/mdz204 [doi] PST - ppublish SO - Ann Oncol. 2019 Sep 1;30(9):1417-1427. doi: 10.1093/annonc/mdz204.