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

Tracy L Stockley; Bryan Lo; Adrian Box; Andrea Gomez Corredor; John DeCoteau; Patrice Desmeules; Harriet Feilotter; Daria Grafodatskaya; Cynthia Hawkins; Weei Yuarn Huang; Iyare Izevbaye; Guylaine Lepine; Andreas I Papadakis; Paul C Park; Brandon S Sheffield; Danh Tran-Thanh; Stephen Yip; Ming Sound Tsao

doi:10.3390/curroncol30040302

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

Curr Oncol. 2023 Mar 31;30(4):3989-3997. doi: 10.3390/curroncol30040302.

Authors

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.

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.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Canada
Consensus
Gene Fusion
High-Throughput Nucleotide Sequencing
Humans
Neoplasms* / drug therapy
Oncogene Proteins, Fusion / genetics
RNA / therapeutic use
Receptor, trkA* / genetics
Receptor, trkA* / therapeutic use

Substances

Receptor, trkA
RNA
Oncogene Proteins, Fusion

Grants and funding

Supported by Bayer Inc. in the capacity of working group meeting support.