ArticleNeoplasia (New York, N.Y.)2016
Somatic Copy Number Amplification and Hyperactivating Somatic Mutations of EZH2 Correlate With DNA Methylation and Drive Epigenetic Silencing of Genes Involved in Tumor Suppression and Immune Responses in Melanoma.
Article in Neoplasia (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 57 citations in OpenAlex.
- Relapse-free survival in a pediatric patient with recurrent EZH2-mutant melanoma treated with adjuvant tazemetostat.NPJ precision oncology · 2025Article
- Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment.Biomolecules · 2025Review
- The epigenetic landscape in intestinal stem cells and its deregulation in colorectal cancer.Stem cells (Dayton, Ohio) · 2024Review
- Novel Prognostic Markers for Skin Cutaneous Melanoma.Clinical, cosmetic and investigational dermatology · 2024Article
- UHRF1/UBE2L6/UBR4-mediated ubiquitination regulates EZH2 abundance and thereby melanocytic differentiation phenotypes in melanoma.Oncogene · 2023Article
- lncRNAs-EZH2 interaction as promising therapeutic target in cutaneous melanoma.Frontiers in molecular biosciences · 2023Review
- The reversion of DNA methylation-induced miRNA silence via biomimetic nanoparticles-mediated gene delivery for efficient lung adenocarcinoma therapy.Molecular cancer · 2022Article
- Machine-learning-optimized Cas12a barcoding enables the recovery of single-cell lineages and transcriptional profiles.Molecular cell · 2022Article
- Characterization of the CpG Island Hypermethylated Phenotype Subclass in Primary Melanomas.The Journal of investigative dermatology · 2022Article
- The clinical significance of adenomatous polyposis coli (APC) and catenin Beta 1 (CTNNB1) genetic aberrations in patients with melanoma.BMC cancer · 2022Article
- Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma.Journal of personalized medicine · 2021Review
- Targeting epigenetic mechanisms to overcome venetoclax resistance.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Association of tumor mutation burden and epidermal growth factor receptor inhibitor history with survival in patients with metastatic stage III/IV non-small-cell lung cancer: A retrospective study.Clinics (Sao Paulo, Brazil) · 2021Article
- Multi-omics approaches in cancer research with applications in tumor subtyping, prognosis, and diagnosis.Computational and structural biotechnology journal · 2021Review
- Epigenetic Mechanisms of Resistance to Immune Checkpoint Inhibitors.Biomolecules · 2020Review
- H3K27me3 and EZH2 expression in melanoma: relevance for melanoma progression and response to immune checkpoint blockade.Clinical epigenetics · 2020Article
- H3K27me3-mediated PGC1α gene silencing promotes melanoma invasion through WNT5A and YAP.The Journal of clinical investigation · 2020Article
- Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation.International journal of molecular sciences · 2018Article
- Distinct prognostic value of mRNA expression of guanylate-binding protein genes in skin cutaneous melanoma.Oncology letters · 2018Article
- Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma.BMC systems biology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The epigenetic modifier EZH2 is in the center of a repressive complex controlling differentiation of normal cells. In cancer EZH2 has been implicated in silencing tumor suppressor genes. Its role in melanoma as well as target genes affected by EZH2 are poorly understood. In view of this we have used an integrated systems biology approach to analyze 471 cases of skin cutaneous melanoma (SKCM) in The Cancer Genome Atlas (TCGA) for mutations and amplifications of EZH2. Identified changes in target genes were validated by interrogation of microarray data from melanoma cells treated with the EZH2 inhibitor GSK126. We found that EZH2 activation by mutations, gene amplification and increased transcription occurred in about 20% of the cohort. These alterations were associated with significant hypermethylation of DNA and significant downregulation of 11% of transcripts in patient RNASeq data. GSK126 treatment of melanoma lines containing EZH2 activation reversed such transcriptional repression in 98 candidate target genes. Gene enrichment analysis revealed genes associated with tumor suppression, cell differentiation, cell cycle inhibition and repression of metastases as well as antigen processing and presentation pathways. The identified changes in EZH2 were associated with an adverse prognosis in the TCGA dataset. These results suggest that inhibiting of EZH2 is a promising therapeutic avenue for a substantial fraction of melanoma patients.
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