4.3 Article

NTRK fusions in osteosarcoma are rare and non-functional events

期刊

JOURNAL OF PATHOLOGY CLINICAL RESEARCH
卷 6, 期 2, 页码 107-112

出版社

WILEY
DOI: 10.1002/cjp2.158

关键词

NTRK; tyrosine kinase inhibitors; osteosarcoma

资金

  1. Swiss National Science Foundation
  2. Foundation of the Basel Bone Tumour Reference Centre
  3. Gertrude von Meissner Stiftung
  4. Stiftung fur krebskranke Kinder, Regio Basiliensis
  5. Swedish Childhood Cancer Fund
  6. Swedish Cancer Society
  7. Swedish Research Council
  8. Faculty of Medicine at Lund University
  9. Ake Wiberg Foundation
  10. Royal Physiographic Society (Lund, Sweden)
  11. Crafoord Foundation
  12. Cura Placida Stiftung

向作者/读者索取更多资源

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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