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Omics · study · 2026

SRF fusion oncogenes encode constitutively activated chimeric transcription factors in myoid soft tissue tumors [MSC_hTERT]

Listed in NCBI GEO

SRF fusion genes result from chromosomal translocations in muscle-related soft tissue tumors, including perivascular tumors, myofibroma and rhabdomyosarcoma.

Description

SRF encodes the Serum Response Factor, a well-characterized transcription factor that dimerizes and associates with the cofactors TCF or MRTF to regulate muscle development. Here, we characterized four SRF fusion genes: SRF::RELA, SRF::FOXO1, SRF::ICA1L and SRF::PDGFRB.

All fusions proteins were nuclear and dimerized through the SRF MADS box. SRF::RELA, SRF::FOXO1, and SRF::ICA1L acted as constitutively active transcription factors, independently of canonical cofactors. Their activity depended on the DNA-binding MADS box of SRF and the transactivation domain of the partner protein.

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We identified a cryptic transactivation domain within cytosolic ICA1L. These three SRF fusions promoted mesenchymal cell proliferation and upregulated muscle-related genes. They are representative of 98% of the identified SRF fusion cases.

In contrast, SRF::PDGFRB activity relied on the tyrosine kinase domain and was sensitive to imatinib. SRF::PDGFRB acted as an oncogene in Ba/F3 cells, activated STAT1 signaling, and induced an interferon-like inflammatory response, in line with the inflammatory myofibroblastic tumor, in which that fusion was identified. In conclusion, SRF fusions constitute a novel family of oncogenes supporting cell proliferation and expression of muscle differentiation markers in myoid soft tissue tumors.

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Life Sciences
Inferred from text
Cancer 65%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE30326013 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title