{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Neil E"],"funding":["RCUK | MRC | Medical Research Foundation","RCUK | Biotechnology and Biological Sciences Research Council","EHE Rare Cancer Charity UK, PhD fellowship to Emily Neil","Biotechnology and Biological Sciences Research Council"],"pagination":["1174"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10657451"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(1)"],"pubmed_abstract":["TAZ::CAMTA1 is a fusion protein found in over 90% of Epithelioid Hemangioendothelioma (EHE), a rare vascular sarcoma with an unpredictable disease course. To date, how TAZ::CAMTA1 initiates tumour formation remains unexplained. To study the oncogenic mechanism leading to EHE initiation, we developed a model system whereby TAZ::CAMTA1 expression is induced by doxycycline in primary endothelial cells. Using this model, we establish that upon TAZ::CAMTA1 expression endothelial cells rapidly enter a hypertranscription state, triggering considerable DNA damage. As a result, TC-expressing cells become trapped in S phase. Additionally, TAZ::CAMTA1-expressing endothelial cells have impaired homologous recombination, as shown by reduced BRCA1 and RAD51 foci formation. Consequently, the DNA damage remains unrepaired and TAZ::CAMTA1-expressing cells enter senescence. Knockout of Cdkn2a, the most common secondary mutation found in EHE, allows senescence bypass and uncontrolled growth. Together, this provides a mechanistic explanation for the clinical course of EHE and offers novel insight into therapeutic options."],"journal":["Communications biology"],"pubmed_title":["The oncogenic fusion protein TAZ::CAMTA1 promotes genomic instability and senescence through hypertranscription."],"pmcid":["PMC10657451"],"funding_grant_id":["BB/R007209/1","MR/P000673/1","MR/T000384/1"],"pubmed_authors":["Pooley O","Neil E","Paredes R","Kouskoff V","Rubin B"],"additional_accession":[]},"is_claimable":false,"name":"The oncogenic fusion protein TAZ::CAMTA1 promotes genomic instability and senescence through hypertranscription.","description":"TAZ::CAMTA1 is a fusion protein found in over 90% of Epithelioid Hemangioendothelioma (EHE), a rare vascular sarcoma with an unpredictable disease course. To date, how TAZ::CAMTA1 initiates tumour formation remains unexplained. To study the oncogenic mechanism leading to EHE initiation, we developed a model system whereby TAZ::CAMTA1 expression is induced by doxycycline in primary endothelial cells. Using this model, we establish that upon TAZ::CAMTA1 expression endothelial cells rapidly enter a hypertranscription state, triggering considerable DNA damage. As a result, TC-expressing cells become trapped in S phase. Additionally, TAZ::CAMTA1-expressing endothelial cells have impaired homologous recombination, as shown by reduced BRCA1 and RAD51 foci formation. Consequently, the DNA damage remains unrepaired and TAZ::CAMTA1-expressing cells enter senescence. Knockout of Cdkn2a, the most common secondary mutation found in EHE, allows senescence bypass and uncontrolled growth. Together, this provides a mechanistic explanation for the clinical course of EHE and offers novel insight into therapeutic options.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2025-04-18T13:13:14.258Z","creation":"2025-02-19T01:52:17.8Z"},"accession":"S-EPMC10657451","cross_references":{"pubmed":["37980390"],"doi":["10.1038/s42003-023-05540-4"]}}