NTRK fusions in osteosarcoma are rare and non-functional events.
- Ameline B Bone Tumour Reference Center at the Institute of Pathology, University and University Hospital Basel, Basel, Switzerland.
- Saba KH Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
- Kovac M Bone Tumour Reference Center at the Institute of Pathology, University and University Hospital Basel, Basel, Switzerland.
- Magnusson L Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
- Witt O Coordinator INFORM Program, Hopp Children's Cancer Center, German Cancer Research Center, University Hospital Heidelberg, Heidelberg, Germany.
- Bielack S Cooperative Osteosarcoma Study Group, Stuttgart Cancer Center, Klinikum Stuttgart - Olgahospital, Pediatrics 5 (Oncology, Hematology, Immunology), Stuttgart, Germany.
- Nathrath M Department of Pediatrics, Pediatric Oncology Center, Technische Universität München, Munich, Germany.
- Nord KH Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
- Baumhoer D Bone Tumour Reference Center at the Institute of Pathology, University and University Hospital Basel, Basel, Switzerland.
- 2020-02-06
Published in:
- The journal of pathology. Clinical research. - 2020
English
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1002/cjp2.158
- PMID 32022484
- Persistent URL
- https://sonar.ch/global/documents/92269
Export to…
Statistics
Document views: 53
File downloads:
- Full-text: 0