| Autor: |
Boutaina Boulouadnine, Laurence de Villenfagne, Christine Galant, Raphael Sciot, Bénédicte Brichard, Jean‐Baptiste Demoulin |
| Přispěvatelé: |
UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - SSS/IREC/SLUC - Pôle St.-Luc |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Genes, chromosomes & cancer, Vol. 61, no. 11, p. 678-682 (2022) |
| ISSN: |
1098-2264 |
| Popis: |
The ETV6::NTRK3 fusion is the most common gene alteration in infantile fibrosarcoma, a soft tissue tumor affecting patients under two years of age. Less frequently, these tumors harbor fusions of genes encoding other kinases, such as BRAF, which activates MEK in the mitogen-activated protein kinase pathway. The identification and characterization of these oncogenes is crucial to facilitate diagnosis, validate new treatments and better understand the pathophysiology of these neoplasms. Herein, we analyzed an ETV6::NTRK3-negative infantile fibrosarcoma from a 5-day-old patient by RNA-sequencing to identify new fusion transcripts. Functional exploration of the fusion of interest was performed by in vitro assays to study its activity, oncogenicity and sensitivity to the MEK inhibitor trametinib. We identified a novel fusion involving the PHIP and BRAF genes. The corresponding fusion protein constitutively activated the mitogen-activated protein kinase pathway, resulting in fibroblast transformation. Treatment of transfected cells with trametinib effectively inhibited signaling by PHIP::BRAF. PHIP::BRAF is a novel fusion oncogene that can be targeted by trametinib in infantile fibrosarcoma. This article is protected by copyright. All rights reserved. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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