title: YAP1 and VGLL3, encoding two cofactors of TEAD transcription factors, are amplified and overexpressed in a subset of soft tissue sarcomas.
abstract: In a series of 404 adult soft tissue sarcomas, analyzed by array-CGH, we have observed in approximately 10% of them a genomic amplification of either chromosome bands 11q22 or 3p12. These two amplicons likely target the YAP1 and VGLL3 genes, respectively. Both genes encode proteins that are cofactors of the TEAD family of transcription factors. Very good correlations between amplification and expression levels were observed. Welch test analyses of transcriptome data demonstrate that tumors with amplicons share a large set of upregulated and downregulated genes. Inhibition of YAP1 and VGLL3 in cell lines with these amplifications/overexpressions leads to similar phenotypes: decrease of proliferation rate, and to a lesser extent decrease of migration properties. These data, and the fact that these amplicons are observed either in de-differentiated liposarcomas or in undifferentiated pleomorphic sarcomas, suggest that these genetics events could be involved in oncogenesis and progression of soft tissue sarcomas.
authors.affiliation: Genetics and Biology of Cancers, Institut Curie, 26 rue d'Ulm, Paris, France.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Hélias-Rodzewicz
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pérot
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chibon
authors.forename: Céline
authors.initials: C
authors.lastname: Ferreira
authors.forename: Pauline
authors.initials: P
authors.lastname: Lagarde
authors.forename: Philippe
authors.initials: P
authors.lastname: Terrier
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Coindre
authors.forename: Alain
authors.initials: A
authors.lastname: Aurias
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D045744:Cell Line, Tumor; D002880:Chromosomes, Human, Pair 11; D002893:Chromosomes, Human, Pair 3; D055028:Comparative Genomic Hybridization; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008080:Liposarcoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012509:Sarcoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051034:Inhibitor of Apoptosis Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; C555441:VGLL3 protein, human; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C494833:BIRC2 protein, human; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases