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NTRK fusions in osteosarcoma are rare and non-functional events

Ameline, Baptiste ; Saba, Karim H. LU orcid ; Kovac, Michal ; Magnusson, Linda LU ; Witt, Olaf ; Bielack, Stefan ; Nathrath, Michaela ; Nord, Karolin H. LU and Baumhoer, Daniel (2020) In Journal of Pathology: Clinical Research 6(2). p.107-112
Abstract

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... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
NTRK, osteosarcoma, tyrosine kinase inhibitors
in
Journal of Pathology: Clinical Research
volume
6
issue
2
pages
6 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85079001985
  • pmid:32022484
ISSN
2056-4538
DOI
10.1002/cjp2.158
language
English
LU publication?
yes
id
b604c9de-c5aa-4756-bcd8-67d68e6ab74a
date added to LUP
2020-02-17 13:51:37
date last changed
2024-05-29 08:18:54
@article{b604c9de-c5aa-4756-bcd8-67d68e6ab74a,
  abstract     = {{<p>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 (&lt;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.</p>}},
  author       = {{Ameline, Baptiste and Saba, Karim H. and Kovac, Michal and Magnusson, Linda and Witt, Olaf and Bielack, Stefan and Nathrath, Michaela and Nord, Karolin H. and Baumhoer, Daniel}},
  issn         = {{2056-4538}},
  keywords     = {{NTRK; osteosarcoma; tyrosine kinase inhibitors}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{107--112}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Pathology: Clinical Research}},
  title        = {{NTRK fusions in osteosarcoma are rare and non-functional events}},
  url          = {{http://dx.doi.org/10.1002/cjp2.158}},
  doi          = {{10.1002/cjp2.158}},
  volume       = {{6}},
  year         = {{2020}},
}