YAP1 and VGLL3, encoding two cofactors of TEAD transcription factors, are amplified and overexpressed in a subset of soft tissue sarcomas
- 14 September 2010
- journal article
- research article
- Published by Wiley in Genes, Chromosomes and Cancer
- Vol. 49 (12), 1161-1171
- https://doi.org/10.1002/gcc.20825
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 dedifferentited liposarcomas or in undifferentiated pleomorphic sarcomas, suggest that these genetics events could be involved in oncogenesis and progression of soft tissue sarcomas.Keywords
This publication has 27 references indexed in Scilit:
- YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferationGenes & Development, 2009
- Strong Smooth Muscle Differentiation Is Dependent on Myocardin Gene Amplification in Most Human Retroperitoneal LeiomyosarcomasCancer Research, 2009
- MMP13, Birc2 (cIAP1), and Birc3 (cIAP2), Amplified on Chromosome 9, Collaborate with p53 Deficiency in Mouse Osteosarcoma ProgressionCancer Research, 2009
- YAP1 is involved in mesothelioma development and negatively regulated by Merlin through phosphorylationCarcinogenesis: Integrative Cancer Research, 2008
- Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth controlGenes & Development, 2007
- Elucidation of a Universal Size-Control Mechanism in Drosophila and MammalsCell, 2007
- JUN Oncogene Amplification and Overexpression Block Adipocytic Differentiation in Highly Aggressive SarcomasCancer Cell, 2007
- Identification of Tumor-Specific Molecular Signatures in Intracranial Ependymoma and Association With Clinical CharacteristicsJournal of Clinical Oncology, 2006
- Identification and Validation of Oncogenes in Liver Cancer Using an Integrative Oncogenomic ApproachCell, 2006
- A Model-Based Background Adjustment for Oligonucleotide Expression ArraysJournal of the American Statistical Association, 2004