Novel COL4A1-VEGFD gene fusion in myofibroma.
FURIN
PDGFRB
VEGF
arresten
collagen type IV
infantile myofibromatosis
myofibroma
perivascular myoid tumour
serum response factor
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
15
03
2021
received:
15
01
2021
accepted:
18
03
2021
pubmed:
9
4
2021
medline:
23
9
2021
entrez:
8
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33830670
doi: 10.1111/jcmm.16502
pmc: PMC8093964
doi:
Substances chimiques
Biomarkers, Tumor
0
COL4A1 protein, human
0
Collagen Type IV
0
VEGFD protein, human
0
Vascular Endothelial Growth Factor D
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4387-4394Subventions
Organisme : Belgian Foundation Against Cancer
ID : 2018-110
Organisme : Action de Recherche Concertée
ID : ARC16/21-073
Informations de copyright
© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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