ArticleMolecular cancer2015
In-depth genomic data analyses revealed complex transcriptional and epigenetic dysregulations of BRAFV600E in melanoma.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- DNA Methylation Classes of Stage II and III Primary Melanomas and Their Clinical and Prognostic Significance.JCO precision oncology · 2024Article
- Mapping the lymph node metastasis landscape: A bibliometric Odyssey of papillary thyroid carcinoma publications (2012-2022).Heliyon · 2024Article
- Characterization of the CpG Island Hypermethylated Phenotype Subclass in Primary Melanomas.The Journal of investigative dermatology · 2022Article
- Targeting TGF-β signal transduction for fibrosis and cancer therapy.Molecular cancer · 2022Review
- SEMA6A/RhoA/YAP axis mediates tumor-stroma interactions and prevents response to dual BRAF/MEK inhibition in BRAF-mutant melanoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Genome-Wide Analysis for the Regulation of Gene Alternative Splicing by DNA Methylation Level in Glioma and its Prognostic Implications.Frontiers in genetics · 2022Article
- Enhancing Therapeutic Approaches for Melanoma Patients Targeting Epigenetic Modifiers.Cancers · 2021Review
- Epigenetically regulated digital signaling defines epithelial innate immunity at the tissue level.Nature communications · 2021Article
- Epigenetics/Epigenomics and Prevention of Early Stages of Cancer by Isothiocyanates.Cancer prevention research (Philadelphia, Pa.) · 2021Review
- Biomarkers in Colorectal Cancer: Current Research and Future Prospects.International journal of molecular sciences · 2020Review
- Genome-Wide Identification and Analysis of the Methylation of lncRNAs and Prognostic Implications in the Glioma.Frontiers in oncology · 2020Article
- KMT2C mediates the estrogen dependence of breast cancer through regulation of ERα enhancer function.Oncogene · 2018Article
- Towards integrated oncogenic marker recognition through mutual information-based statistically significant feature extraction: an association rule mining based study on cancer expression and methylation profiles.Quantitative biology (Beijing, China) · 2017Article
- Comparison of Five Different Assays for the Detection of BRAF Mutations in Formalin-Fixed Paraffin Embedded Tissues of Patients with Metastatic Melanoma.Molecular diagnosis & therapy · 2017Article
- ALDH1A1 and HLTF modulate the activity of lysosomal autophagy inhibitors in cancer cells.Autophagy · 2017Article
- Transcriptome- and proteome-oriented identification of dysregulated eIF4G, STAT3, and Hippo pathways altered by PIK3CABreast cancer research and treatment · 2016Article
- An integrative genomics approach for identifying novel functional consequences of PBRM1 truncated mutations in clear cell renal cell carcinoma (ccRCC).BMC genomics · 2016Article
- Epigenetic mechanisms involved in melanoma pathogenesis and chemoresistance.Annals of translational medicine · 2015Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe recurrent BRAF driver mutation V600E (BRAF (V600E)) is currently one of the most clinically relevant mutations in melanoma. However, the genome-wide transcriptional and epigenetic dysregulations induced by BRAF (V600E) are still unclear. The investigation of this driver mutation's functional consequences is critical to the understanding of tumorigenesis and the development of therapeutic strategies. METHODS AND
resultsWe performed an integrative analysis of transcriptomic and epigenomic changes disturbed by BRAF (V600E) by comparing the gene expression and methylation profiles of 34 primary cutaneous melanoma tumors harboring BRAF (V600E) with those of 27 BRAF (WT) samples available from The Cancer Genome Atlas (TCGA). A total of 711 significantly differentially expressed genes were identified as putative BRAF (V600E) target genes. Functional enrichment analyses revealed the transcription factor MITF (p < 3.6 × 10(-16)) and growth factor TGFB1 (p < 3.1 × 10(-9)) were the most significantly enriched up-regulators, with MITF being significantly up-regulated, whereas TGFB1 was significantly down-regulated in BRAF (V600E), suggesting that they may mediate tumorigenesis driven by BRAF (V600E). Further investigation using the MITF ChIP-Seq data confirmed that BRAF (V600E) led to an overall increased level of gene expression for the MITF targets. Furthermore, DNA methylation analysis revealed a global DNA methylation loss in BRAF (V600E) relative to BRAF (WT). This might be due to BRAF dysregulation of DNMT3A, which was identified as a potential target with significant down-regulation in BRAF (V600E). Finally, we demonstrated that BRAF (V600E) targets may play essential functional roles in cell growth and proliferation, measured by their effects on melanoma tumor growth using a short hairpin RNA silencing experimental dataset.
conclusionsOur integrative analysis identified a set of BRAF (V600E) target genes. Further analyses suggested a complex mechanism driven by mutation BRAF (V600E) on melanoma tumorigenesis that disturbs specific cancer-related genes, pathways, and methylation modifications.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.