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

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.

Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges

“…However, the type of cancer tested and the type of panel used to assess TMB can significantly affect the outcome ( Merino et al, 2020 ). Among the many examples of targeted panels used in the clinical setting there are MyeloSeq, a 40-gene targeted panel used to determine variant and allele frequencies in patients with suspected hematologic malignancies ( Barnell et al, 2021 ), the Oncomine Precision Assay, which tests 45 cancer-related genes (such as EGFR, KRAS, ALK, RET, BRAF, and others) used in screening for genomic alterations that can be treated with targeted therapy in NSCLC, colorectal cancer, melanoma, breast cancer, and other malignancies ( Werner et al, 2022 ; Nindra et al, 2023 ), and other targeted panels such as the TruSight Oncology, the AmpliSeq, the FusionPlex, the QIASeq Multimodal Lung, which have demonstrated expertise in identifying genetic variants, and the NTRK gene fusion panel used to identify tumors sensitive to larotrectinib, an NTRK inhibitor ( Drilon et al, 2018 ; Stockley et al, 2023 ).…”