Insertion of the CXXC domain of KMT2A into YAP1 : An unusual mechanism behind the formation of a chimeric oncogenic protein
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Le résumé fourni par la source
Most neoplasia-associated gene fusions are formed through the fusion of the 5'-part of one gene with the 3'-part of another. We here describe a unique mechanism, by which a part of the KMT2A gene through an insertion replaces part of the YAP1 gene. The resulting YAP1::KMT2A::YAP1 (YKY) fusion was verified by RT-PCR in three cases of sarcoma morphologically resembling sclerosing epithelioid fibrosarcoma (SEF-like sarcoma). In all cases, a portion (exons 4/5-6) encoding the CXXC domain of KMT2A was inserted between exon 4/5 and exon 8/9 of YAP1. The inserted sequence from KMT2A thus replaced exons 5/6-8 of YAP1, which encode an important regulatory sequence of YAP1. To evaluate the cellular impact of the YKY fusion, global gene expression profiles from fresh frozen and formalin-fixed YKY-expressing sarcomas were compared with control tumors. The effects of the YKY fusion, as well as YAP1::KMT2A and KMT2A::YAP1 fusion constructs, were further studied in immortalized fibroblasts. Analysis of differentially upregulated genes revealed significant overlap between tumors and cell lines expressing YKY, as well as with previously reported YAP1 fusions. Pathway analysis of upregulated genes in cells and tumors expressing YKY revealed an enrichment of genes included in key oncogenic signaling pathways, such as Wnt and Hedgehog. As these pathways are known to interact with YAP1, it seems likely that the pathogenesis of sarcomas with the YKY fusion is linked to distorted YAP1 signaling.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Insertion of the <scp>CXXC</scp> domain of <scp>KMT2A</scp> into <scp>YAP1</scp>: An unusual mechanism behind the formation of a chimeric oncogenic protein
- Date Crossref
- 29/05/2023
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Lund University Division of Clinical Genetics pays non établi dans la noticeUniversité ou école supérieure
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Radboud University Nijmegen pays non établi dans la noticeUniversité ou école supérieure
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Radboud University Medical Center Department of Pathology pays non établi dans la noticeOrganisme public
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Sahlgrenska University Hospital Department Clinical Pathology and Genetics pays non établi dans la noticeÉtablissement de santé
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Pediatrics and Genetics pays non établi dans la noticeÉtablissement de santé
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Division of Laboratory Medicine pays non établi dans la noticeStructure de recherche
Division of Clinical Genetics — Lund University, Radboud University Nijmegen et Department of Pathology — Radboud University Medical Center, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.