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An oncogenic role for ETV1 in melanoma.

ABSTRACT: Copy gains involving chromosome 7p represent one of the most common genomic alterations found in melanomas, suggesting the presence of "driver" cancer genes. We identified several tumor samples that harbored focal amplifications situated at the peak of common chromosome 7p gains, in which the minimal common overlapping region spanned the ETV1 oncogene. Fluorescence in situ hybridization analysis revealed copy gains spanning the ETV1 locus in >40% of cases, with ETV1 amplification (>6 copies/cell) present in 13% of primary and 18% of metastatic melanomas. Melanoma cell lines, including those with ETV1 amplification, exhibited dependency on ETV1 expression for proliferation and anchorage-independent growth. Moreover, overexpression of ETV1 in combination with oncogenic NRAS(G12D) transformed primary melanocytes and promoted tumor formation in mice. ETV1 overexpression elevated microphthalmia-associated transcription factor expression in immortalized melanocytes, which was necessary for ETV1-dependent oncogenicity. These observations implicate deregulated ETV1 in melanoma genesis and suggest a pivotal lineage dependency mediated by oncogenic ETS transcription factors in this malignancy.

SUBMITTER: Jane-Valbuena J

PROVIDER: S-EPMC2846410 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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An oncogenic role for ETV1 in melanoma.

Jané-Valbuena Judit J Widlund Hans R HR Perner Sven S Johnson Laura A LA Dibner Aurora C AC Lin William M WM Baker Alissa C AC Nazarian Rosalynn M RM Vijayendran Krishna G KG Sellers William R WR Hahn William C WC Duncan Lyn M LM Rubin Mark A MA Fisher David E DE Garraway Levi A LA

Cancer research 20100216 5

Copy gains involving chromosome 7p represent one of the most common genomic alterations found in melanomas, suggesting the presence of "driver" cancer genes. We identified several tumor samples that harbored focal amplifications situated at the peak of common chromosome 7p gains, in which the minimal common overlapping region spanned the ETV1 oncogene. Fluorescence in situ hybridization analysis revealed copy gains spanning the ETV1 locus in >40% of cases, with ETV1 amplification (>6 copies/cell ...[more]

PMID: 20160028

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Project description:BackgroundPhosphatidylinositol binding clathrin assembly protein interacting mitotic regulator (PIMREG) plays a significant role in metaphase-to-anaphase transition in cell cycle. Its aberrant expression has been reported to be in correlation with the development of several tumors. However, its role in melanoma remains unknown. This study aimed to investigate the diagnostic and prognostic roles of PIMREG in skin cutaneous melanoma (SKCM).MethodsThe expression levels of PIMREG were analyzed in SKCM using datasets downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO). The diagnostic accuracy was assessed using the receiver operating characteristic (ROC) curve. PIMREG was correlated to the functional states of SKCM cells using CancerSEA. Additionally, a protein-protein interaction network was constructed using STRING (https://cn.string-db.org), and hub genes were identified using Cytoscape. Enrichment analysis through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) was utilized to explore the potential functions of PIMREG. The single-sample GSEA (ssGSEA) method was employed to investigate the correlation between PIMREG expression and the level of immune infiltration in SKCM. Drug sensitivity and resistance were analyzed using GSCALite and Cellminer.ResultsThe expression of PIMREG was significantly higher in SKCM tissues. Its overexpression correlated with poor survival outcome in melanoma patients. ROC analysis also revealed that PIMREG had high diagnostic potential, with area under the ROC curve (AUC) value of 0.874. Multivariate regression also identified PIMREG could serve as an independent diagnostic indicator for SKCM. Using the web tool of CancerSEA, we demonstrated that PIMREG is involved in cell cycle, DNA repair, DNA damage, epithelial-mesenchymal transition (EMT), invasion, and proliferation. Functional enrichment analysis revealed that PIMREG might be correlated with some biological processes (BPs) and important pathways related to cancer, including Wnt signaling and epidermis development.ConclusionsPIMREG is a promising diagnostic and prognostic biomarker and may be regarded as a possible therapeutic target for SKCM.

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An oncogenic role for ETV1 in melanoma.

Publications

An oncogenic role for ETV1 in melanoma.

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