Consensus Recommendations to Optimize the Detection and Reporting of NTRK Gene Fusions by RNA-Based Next-Generation Sequencing

Tracy L Stockley^{1

2

3}, Bryan Lo⁴, Adrian Box⁵, Andrea Gomez Corredor⁶, John DeCoteau⁷, Patrice Desmeules⁸, Harriet Feilotter^{9

10}, Daria Grafodatskaya^{11

12}, Cynthia Hawkins^{2

13}, Weei Yuarn Huang^{2

14

15}, Iyare Izevbaye¹⁶, Guylaine Lepine¹⁷, Andreas I Papadakis¹⁸, Paul C Park¹⁹, Brandon S Sheffield²⁰, Danh Tran-Thanh²¹, Stephen Yip^{22

23}, Ming Sound Tsao^{1

2}

Affiliations

¹ Laboratory Medicine Program, University Health Network, Toronto, ON M5G 2C4, Canada.
² Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5R 0A3, Canada.
³ Advanced Molecular Diagnostics Laboratory, Princess Margaret Cancer Centre, Toronto, ON M5G 2C1, Canada.
⁴ Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON K1H 8L6, Canada.
⁵ Alberta Precision Laboratories, Calgary, AB T2N 7A4, Canada.
⁶ McGill University Health Center, Montreal, QC H4A 3J1, Canada.
⁷ Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5A9, Canada.
⁸ IUCPQ-UL, Quebec Heart and Lung Institute, Quebec City, QC G1V 4G5, Canada.
⁹ Kingston Health Sciences Centre, Kingston, ON K7L 2V7, Canada.
¹⁰ Department of Pathology and Molecular Medicine, Queens University, Kingston, ON K7L 3N6, Canada.
¹¹ Hamilton Health Sciences Centre, Hamilton, ON L9C 1C4, Canada.
¹² Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada.
¹³ Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
¹⁴ Nova Scotia Health Authority, Halifax, NS B3H 2E2, Canada.
¹⁵ Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
¹⁶ Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R7, Canada.
¹⁷ Hopital Maisonneuve-Rosemont, Montreal, QC H1T 2M4, Canada.
¹⁸ Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
¹⁹ Shared Health Manitoba, Winnipeg, MB R3A 1R9, Canada.
²⁰ William Osler Health System, Brampton, ON L6R 3J7, Canada.
²¹ CHUM-Centre Hospitalier de l'Universite de Montreal, Montreal, QC H3T 1J4, Canada.
²² BC Cancer, Vancouver, BC V5Z 4S6, Canada.
²³ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.

PMID: 37185415
PMCID: PMC10136625
DOI: 10.3390/curroncol30040302

Review

Consensus Recommendations to Optimize the Detection and Reporting of NTRK Gene Fusions by RNA-Based Next-Generation Sequencing

Tracy L Stockley et al. Curr Oncol. 2023.

. 2023 Mar 31;30(4):3989-3997.

doi: 10.3390/curroncol30040302.

Authors

Affiliations

¹ Laboratory Medicine Program, University Health Network, Toronto, ON M5G 2C4, Canada.
² Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5R 0A3, Canada.
³ Advanced Molecular Diagnostics Laboratory, Princess Margaret Cancer Centre, Toronto, ON M5G 2C1, Canada.
⁴ Department of Pathology and Laboratory Medicine, The Ottawa Hospital, Ottawa, ON K1H 8L6, Canada.
⁵ Alberta Precision Laboratories, Calgary, AB T2N 7A4, Canada.
⁶ McGill University Health Center, Montreal, QC H4A 3J1, Canada.
⁷ Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5A9, Canada.
⁸ IUCPQ-UL, Quebec Heart and Lung Institute, Quebec City, QC G1V 4G5, Canada.
⁹ Kingston Health Sciences Centre, Kingston, ON K7L 2V7, Canada.
¹⁰ Department of Pathology and Molecular Medicine, Queens University, Kingston, ON K7L 3N6, Canada.
¹¹ Hamilton Health Sciences Centre, Hamilton, ON L9C 1C4, Canada.
¹² Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada.
¹³ Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
¹⁴ Nova Scotia Health Authority, Halifax, NS B3H 2E2, Canada.
¹⁵ Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
¹⁶ Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R7, Canada.
¹⁷ Hopital Maisonneuve-Rosemont, Montreal, QC H1T 2M4, Canada.
¹⁸ Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
¹⁹ Shared Health Manitoba, Winnipeg, MB R3A 1R9, Canada.
²⁰ William Osler Health System, Brampton, ON L6R 3J7, Canada.
²¹ CHUM-Centre Hospitalier de l'Universite de Montreal, Montreal, QC H3T 1J4, Canada.
²² BC Cancer, Vancouver, BC V5Z 4S6, Canada.
²³ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.

PMID: 37185415
PMCID: PMC10136625
DOI: 10.3390/curroncol30040302

Abstract

The detection of gene fusions by RNA-based next-generation sequencing (NGS) is an emerging method in clinical genetic laboratories for oncology biomarker testing to direct targeted therapy selections. A recent Canadian study (CANTRK study) comparing the detection of NTRK gene fusions on different NGS assays to determine subjects' eligibility for tyrosine kinase TRK inhibitor therapy identified the need for recommendations for best practices for laboratory testing to optimize RNA-based NGS gene fusion detection. To develop consensus recommendations, representatives from 17 Canadian genetic laboratories participated in working group discussions and the completion of survey questions about RNA-based NGS. Consensus recommendations are presented for pre-analytic, analytic and reporting aspects of gene fusion detection by RNA-based NGS.

Keywords: NTRK gene fusions; molecular pathology; next generation RNA sequencing; oncology.

PubMed Disclaimer

Conflict of interest statement

T.S.L. is on advisory boards for AstraZeneca, Astellas, Amgen, Bayer, Pfizer, Novartis, Janssen and Merck and received research funding AstraZeneca; B.L. is on advisory boards for AstraZeneca, Bayer, Novartis and Pfizer. J.D. is on advisory boards for Novartis, Bayer and Thermo Fisher. P.D. is on advisory boards for AstraZeneca, Bristol-Myers Squibb, Pfizer, Bayer and Eli Lilly and received research support from Pfizer, Novartis, Roche, Eli Lilly, EMD Serrono, Bayer and AstraZeneca. H.F. is on advisory boards for AstraZeneca, Bayer, Novartis and Pfizer and received research funding from EMD Serono, Amgen, AstraZeneca, Pfizer and Roche. W.Y.H. is on the advisory board for Bayer and received research funding from Pfizer. I.I. is on advisory boards for AstraZeneca, Bayer, Novartis, Pfizer and Roche. D.G. is on advisory boards for Bayer, Pfizer, Novartis and Jansse, received validation funding from Pfizer, and speaker honorarium from Thermo Fisher. S.Y. is on advisory boards for Amgen, AstraZeneca, Bayer, Incyte and Roche. P.P. is on advisory boards for Bayer and Novartis. M.S.T. is on advisory boards for Bayer, Amgen, AstraZeneca, Daiichi-Sankyo, Abbvie and Sanofi/Regeneron and received research funding from Bayer, AstraZeneca and Sanofi.

References

1. Yip S., Christofides A., Banerji S., Downes M.R., Izevbaye I., Lo B., MacMillan A., McCuaig J., Stockley T., Yousef G.M., et al. A Canadian Guideline on the Use of next-Generation Sequencing in Oncology. Curr. Oncol. 2019;26:e241–e254. doi: 10.3747/co.26.4731. - DOI - PMC - PubMed
1. Stockley T.L., Lo B., Box A., Corredor A.G., DeCoteau J., Desmeules P., Feilotter H., Grafodatskaya D., Greer W., Hawkins C., et al. CANTRK: A Canadian Ring Study to Optimize Detection of NTRK Gene Fusions by Next-Generation RNA Sequencing. J. Mol. Diagn. 2022;25:168–174. doi: 10.1016/j.jmoldx.2022.12.004. - DOI - PubMed
1. Hsiao S.J., Zehir A., Sireci A.N., Aisner D.L. Detection of Tumor NTRK Gene Fusions to Identify Patients Who May Benefit from Tyrosine Kinase (TRK) Inhibitor Therapy. J. Mol. Diagn. 2019;21:553–571. doi: 10.1016/j.jmoldx.2019.03.008. - DOI - PMC - PubMed
1. Marchiò C., Scaltriti M., Ladanyi M., Iafrate A.J., Bibeau F., Dietel M., Hechtman J.F., Troiani T., López-Rios F., Douillard J.-Y., et al. ESMO Recommendations on the Standard Methods to Detect NTRK Fusions in Daily Practice and Clinical Research. Ann. Oncol. 2019;30:1417–1427. doi: 10.1093/annonc/mdz204. - DOI - PubMed
1. Solomon J.P., Benayed R., Hechtman J.F., Ladanyi M. Identifying Patients with NTRK Fusion Cancer. Ann. Oncol. 2019;30((Suppl. S8)):viii16–viii22. doi: 10.1093/annonc/mdz384. - DOI - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Consensus Recommendations to Optimize the Detection and Reporting of NTRK Gene Fusions by RNA-Based Next-Generation Sequencing

Affiliations

Consensus Recommendations to Optimize the Detection and Reporting of NTRK Gene Fusions by RNA-Based Next-Generation Sequencing

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical