RNA-sequencing of myxoinflammatory fibroblastic sarcomas reveals a novel SND1::BRAF fusion and 3 different molecular aberrations with the potential to upregulate the TEAD1 gene including SEC23IP::VGLL3 and TEAD1::MRTFB gene fusions

Klubickova N, Agaimy A, Hajkova V, Ptakova N, Grossmann P, Steiner P, Michal M, Michal M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Virchows Archiv Springer Verlag (Germany)

DOI: 10.1007/s00428-022-03368-7

Abstract

Myxoinflammatory fibroblastic sarcoma (MIFS) has been shown to harbor various recurrent molecular aberrations; most of which, however, seem to be present in only a minority of cases. In order to better characterize the molecular underpinnings of MIFS, fourteen cases were analyzed by targeted RNA-sequencing (RNA-seq), VGLL3 enumeration FISH probe, and BRAF break-apart and enumeration probes. Neither t(1;10)(p22;q24) nor BRAF gene amplifications were found. However, VGLL3 gene amplification was detected in 5 cases by FISH which corresponded with an increase in VGLL3 expression detected by RNA-seq. In 1 of these cases, RNA-seq additionally revealed a novel SND1::BRAF fusion. Two of the 9 cases lacking VGLL3 amplification harbored either a SEC23IP::VGLL3 or a TEAD1::MRTFB rearrangement by RNA-seq, both confirmed by RT-PCR and Sanger sequencing. The detected molecular aberrations have a potential to either activate the expression of genes regulated by the transcription factors of the TEAD family, which are involved in tumor initiation and progression, or switch on the MEK/ERK signaling cascade, which plays an important role in cell cycle progression. Our results broaden the molecular genetic spectrum of MIFS and point toward the importance of the VGLL3-TEAD interaction, as well as the deregulation of the MEK/ERK pathway in the pathogenesis of MIFS, and may represent a potential target for therapy of recurrent or advanced disease.

Authors with CRIS profile

Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Biopticka laborator s.r.o. CZ Czech Republic (CZ) Univerzita Karlova v Praze / Charles University in Prague CZ Czech Republic (CZ)

How to cite

APA:

Klubickova, N., Agaimy, A., Hajkova, V., Ptakova, N., Grossmann, P., Steiner, P.,... Michal, M. (2022). RNA-sequencing of myxoinflammatory fibroblastic sarcomas reveals a novel SND1::BRAF fusion and 3 different molecular aberrations with the potential to upregulate the TEAD1 gene including SEC23IP::VGLL3 and TEAD1::MRTFB gene fusions. Virchows Archiv. https://doi.org/10.1007/s00428-022-03368-7

MLA:

Klubickova, Natalie, et al. "RNA-sequencing of myxoinflammatory fibroblastic sarcomas reveals a novel SND1::BRAF fusion and 3 different molecular aberrations with the potential to upregulate the TEAD1 gene including SEC23IP::VGLL3 and TEAD1::MRTFB gene fusions." Virchows Archiv (2022).

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