NTRK fusions in osteosarcoma are rare and non-functional events

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


Neurotrophic tyrosine receptor kinase (NTRK) fusions are promising molecular targets that have been described in a broad range of malignant tumours. Fusions commonly lead to the expression of chimeric proteins with constitutive tyrosine kinase activation that drives tumorigenesis. Despite a low prevalence among most solid tumours (<1%), the first encouraging results with pan-NTRK tyrosine kinase inhibitors (TKIs) such as larotrectinib or entrectinib stimulated the search for eligible patients. Here, we report the first three cases of osteosarcoma harbouring NTRK fusions, among 113 patients sequenced. It is also the first report on NTRK fusions within a tumour type characterised by highly rearranged genomes and abundant passenger mutations. Whereas the presence of NTRK gene fusions in many tumours is considered to be one of the main driver events for tumour progression, the three chimeric transcripts described here appear non-functional and likely represent randomly occurring passenger alterations. Particularly in tumours with complex karyotypes, it may therefore be advisable to specifically investigate the fusion transcripts for functional impact before considering targeted treatment approaches using pan-NTRK TKIs.


Enheter & grupper
Externa organisationer
  • University Hospital Heidelberg
  • Klinikum Stuttgart Olgahospital
  • Technical University of Munich
  • University Hospital Basel

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik


Sidor (från-till)107-112
Antal sidor6
TidskriftJournal of Pathology: Clinical Research
Utgåva nummer2
Tidigt onlinedatum2020
StatusPublished - 2020 apr
Peer review utfördJa

Relaterad forskningsoutput

Karim Saba, 2020 nov 20, Lund: Lund University, Faculty of Medicine. 67 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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