Identification of a novel PHIP::BRAF gene fusion in infantile fibrosarcoma.
Genes Chromosomes Cancer
; 61(11): 678-682, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-35672277
ABSTRACT
INTRODUCTION:
The ETV6NTRK3 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 are crucial to facilitate diagnosis, validate new treatments, and better understand the pathophysiology of these neoplasms.METHODS:
Herein, we analyzed an ETV6NTRK3-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.RESULTS:
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 PHIPBRAF.CONCLUSION:
PHIPBRAF is a novel fusion oncogene that can be targeted by trametinib in infantile fibrosarcoma.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Fusão Oncogênica
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Neoplasias Musculares
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Proteínas Proto-Oncogênicas B-raf
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Peptídeos e Proteínas de Sinalização Intracelular
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Fibrossarcoma
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
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Male
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Newborn
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article