Novel COL4A1-VEGFD gene fusion in myofibroma.
J Cell Mol Med
; 25(9): 4387-4394, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33830670
ABSTRACT
Myofibroma is a benign pericytic tumour affecting young children. The presence of multicentric myofibromas defines infantile myofibromatosis (IMF), which is a life-threatening condition when associated with visceral involvement. The disease pathophysiology remains poorly characterized. In this study, we performed deep RNA sequencing on eight myofibroma samples, including two from patients with IMF. We identified five different in-frame gene fusions in six patients, including three previously described fusion transcripts, SRF-CITED1, SRF-ICA1L and MTCH2-FNBP4, and a fusion of unknown significance, FN1-TIMP1. We found a novel COL4A1-VEGFD gene fusion in two cases, one of which also carried a PDGFRB mutation. We observed a robust expression of VEGFD by immunofluorescence on the corresponding tumour sections. Finally, we showed that the COL4A1-VEGFD chimeric protein was processed to mature VEGFD growth factor by proteases, such as the FURIN proprotein convertase. In conclusion, our results unravel a new recurrent gene fusion that leads to VEGFD production under the control of the COL4A1 gene promoter in myofibroma. This fusion is highly reminiscent of the COL1A1-PDGFB oncogene associated with dermatofibrosarcoma protuberans. This work has implications for the diagnosis and, possibly, the treatment of a subset of myofibromas.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
/
Regulação Neoplásica da Expressão Gênica
/
Colágeno Tipo IV
/
Fator D de Crescimento do Endotélio Vascular
/
Miofibroma
/
Fusão Gênica
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Cell Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Bélgica