NTRK1 Fusions identified by non-invasive plasma next-generation sequencing (NGS) across 9 cancer types
Background Activating fusions of the NTRK1 , NTRK2 and NTRK3 genes are drivers of carcinogenesis and proliferation across a broad range of tumour types in both adult and paediatric patients. Recently, the FDA granted tumour-agnostic approvals of TRK inhibitors, larotrectinib and entrectinib, based o...
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Veröffentlicht in: | British journal of cancer 2022-02, Vol.126 (3), p.514-520 |
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Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Background
Activating fusions of the
NTRK1
,
NTRK2
and
NTRK3
genes are drivers of carcinogenesis and proliferation across a broad range of tumour types in both adult and paediatric patients. Recently, the FDA granted tumour-agnostic approvals of TRK inhibitors, larotrectinib and entrectinib, based on significant and durable responses in multiple primary tumour types. Unfortunately, testing rates in clinical practice remain quite low. Adding plasma next-generation sequencing of circulating tumour DNA (ctDNA) to tissue-based testing increases the detection rate of oncogenic drivers and demonstrates high concordance with tissue genotyping. However, the clinical potential of ctDNA analysis to identify
NTRK
fusion-positive tumours has been largely unexplored.
Methods
We retrospectively reviewed a ctDNA database in advanced stage solid tumours for
NTRK1
fusions.
Results
NTRK1
fusion events, with nine unique fusion partners, were identified in 37 patients. Of the cases for which clinical data were available, 44% had tissue testing for
NTRK1
fusions; the
NTRK1
fusion detected by ctDNA was confirmed in tissue in 88% of cases. Here, we report for the first time that minimally-invasive plasma NGS can detect
NTRK
fusions with a high positive predictive value.
Conclusion
Plasma ctDNA represents a rapid, non-invasive screening method for this rare genomic target that may improve identification of patients who can benefit from TRK-targeted therapy and potentially identify subsequent on- and off-target resistance mechanisms. |
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ISSN: | 0007-0920 1532-1827 1532-1827 |
DOI: | 10.1038/s41416-021-01536-1 |