Aberrant methylation patterns in cancer: a clinical view

Paska, Alja Videtič; Hudler, Petra

doi:10.11613/bm.2015.017

Cited by 85 publications

(45 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is growing evidence demonstrating that DNA methylation may deeply alter protein expression and potentially be a causative event in cancer (Fernandez et al 2012;Jones and Baylin 2002). Hypermethylation has been associated to the silencing of genes and to decreased gene expression of tumour suppressors, whilst hypomethylation can potentially result in genomic instability and reactivation of oncogenes (Litovkin et al 2014(Litovkin et al , 2015Paska and Hudler 2015;Weisenberger 2014). Based on genome-wide studies, abnormal methylation patterns have been detected in melanoma patients, highlighting potential markers for disease progression and also providing an important strategy for tumour diagnosis and treatment (Fu et al 2017;Guo et al 2018;Koga et al 2009).…”

Section: Linking Genes To Protein Expression and Functionmentioning

confidence: 99%

Clinical protein science in translational medicine targeting malignant melanoma

et al. 2019

View full text Add to dashboard Cite

Melanoma of the skin is the sixth most common type of cancer in Europe and accounts for 3.4% of all diagnosed cancers. More alarming is the degree of recurrence that occurs with approximately 20% of patients lethally relapsing following treatment. Malignant melanoma is a highly aggressive skin cancer and metastases rapidly extend to the regional lymph nodes (stage 3) and to distal organs (stage 4). Targeted oncotherapy is one of the standard treatment for progressive stage 4 melanoma, and BRAF inhibitors (e.g. vemurafenib, dabrafenib) combined with MEK inhibitor (e.g. trametinib) can effectively counter BRAFV600E-mutated melanomas. Compared to conventional chemotherapy, targeted BRAFV600E inhibition achieves a significantly higher response rate. After a period of cancer control, however, most responsive patients develop resistance to the therapy and lethal progression. The many underlying factors potentially causing resistance to BRAF inhibitors have been extensively studied. Nevertheless, the remaining unsolved clinical questions necessitate alternative research approaches to address the molecular mechanisms underlying metastatic and treatment-resistant melanoma. In broader terms, proteomics can address clinical questions far beyond the reach of genomics, by measuring, i.e. the relative abundance of protein products, post-translational modifications (PTMs), protein localisation, turnover, protein interactions and protein function. More specifically, proteomic analysis of body fluids and tissues in a given medical and clinical setting can aid in the identification of cancer biomarkers and novel therapeutic targets. Achieving this goal requires the development of a robust and reproducible clinical proteomic platform that encompasses automated biobanking of patient samples, tissue sectioning and histological examination, efficient protein extraction, enzymatic digestion, mass spectrometry-based quantitative protein analysis by label-free or labelling technologies and/or enrichment of peptides with specific PTMs. By combining data from, e.g. phosphoproteomics and acetylomics, the protein expression profiles of different melanoma stages can provide a solid framework for understanding the biology and progression of the disease. When complemented by proteogenomics, customised protein sequence databases generated from patient-specific genomic and transcriptomic data aid in interpreting clinical proteomic biomarker data to provide a deeper and more comprehensive molecular characterisation of cellular

show abstract

Section: Linking Genes To Protein Expression and Functionmentioning

confidence: 99%

Clinical protein science in translational medicine targeting malignant melanoma

et al. 2019

View full text Add to dashboard Cite

show abstract

“…DNA hypermethylation has been well characterized as a signature mode of regulation for cancer cell[171–174]. DNA methylation typically involves methylation of cytosine within CpG-rich regions that are prominently present in promoter regions of tumor suppressor genes such as cyclin-dependent kinase inhibitor 2A (CDKN2A) and BRCA1[172, 175], and typically results in reduced expression of these genes.…”

Section: Epigenetic Silencing Of Duox In Cancermentioning

confidence: 99%

Paradoxical roles of dual oxidases in cancer biology

Little

Sulovari

Danyal

et al. 2017

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Dysregulated oxidative metabolism is a well-recognized aspect of cancer biology, and many therapeutic strategies are based on targeting cancers by altering cellular redox pathways. The NADPH oxidases (NOXes) present an important enzymatic source of biological oxidants, and the expression and activation of several NOX isoforms are frequently dysregulated in many cancers. Cell-based studies have demonstrated a role for several NOX isozymes in controlling cell proliferation and/or cell migration, further supporting a potential contributing role for NOX in promoting cancer. While various NOX isoforms are often upregulated in cancers, paradoxical recent findings indicate that dual oxidases (DUOXes), normally prominently expressed in epithelial lineages, are frequently suppressed in epithelial-derived cancers by epigenetic mechanisms, although the functional relevance of such DUOX silencing has remained unclear. This review will briefly summarize our current understanding regarding the importance of reactive oxygen species (ROS) and NOXes in cancer biology, and focus on recent observations indicating the unique and seemingly opposing roles of DUOX enzymes in cancer biology. We will discuss current knowledge regarding the functional properties of DUOX, and recent studies highlighting mechanistic consequences of DUOX1 loss in lung cancer, and its consequences for tumor invasiveness and current anticancer therapy. Finally, we will also discuss potentially unique roles for the DUOX maturation factors. Overall, a better understanding of mechanisms that regulate DUOX and the functional consequences of DUOX silencing in cancer may offer valuable new diagnostic insights and novel therapeutic opportunities.

show abstract

“…5-methyl-cytosine (m5Cyt) is the most investigated epigenetic modification, and alterations in genomic DNA methylation patterns have been confirmed to be associated with the development of pathological processes and diseases, including cancer (9,10). It has also been reported that DNA methylation patterns can be altered by medication, nutrients and chemicals (11–13).…”

Section: Introductionmentioning

confidence: 99%

Effects of R type and S type ginsenoside Rg3 on DNA methylation in human hepatocarcinoma cells

Teng

Wang

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

Ginsenoside Rg3, a bioactive constituent isolated from Panax ginseng, exhibits antitumorigenic, antioxidative, antiangiogenic, neuroprotective and other biological activities are associated with the regulation of multiple genes. DNA methylation patterns, particularly those in the promoter region, affect gene expression, and DNA methylation is catalyzed by DNA methylases. However, whether ginsenoside Rg3 affects DNA methylation is unknown. High performance liquid chromatography assay, MspI/HpaII polymerase chain reaction (PCR) and reverse transcription-quantitative PCR were performed to assess DNA methylation. It was demonstrated that 20(S)-ginsenoside Rg3 treatment resulted in increased inhibition of cell growth, compared with treatment with 20(R)-ginsenoside Rg3 in the human HepG2 hepatocarcinoma cell line. It was additionally revealed that treatment with 20(S)-ginsenoside Rg3 reduced global genomic DNA methylation, altered cystosine methylation of the promoter regions of P53, B cell lymphoma 2 and vascular endothelial growth factor, and downregulated the expression of DNA methyltransferase (DNMT) 3a and DNMT3b more than treatment with 20(R)-ginsenoside Rg3 in HepG2 cells. These results revealed that the modulation of DNA methylation may be important in the pharmaceutical activities of ginsenoside Rg3.

show abstract

Aberrant methylation patterns in cancer: a clinical view

Cited by 85 publications

References 100 publications

Clinical protein science in translational medicine targeting malignant melanoma

Clinical protein science in translational medicine targeting malignant melanoma

Paradoxical roles of dual oxidases in cancer biology

Effects of R type and S type ginsenoside Rg3 on DNA methylation in human hepatocarcinoma cells

Contact Info

Product

Resources

About