User:AAR3643/Epigenetics of melanoma

Article Draft

Summary

I am proposing to make edits to the article Epigenetics and melanoma. This article is rated as Mid-importance and C-class in quality rating under WikiProject Genetics, and as a result, I believe that some changes could be made to further the discussions of the article and make them more complete. One of the changes I proposed upon reading the review article regarding epigenetics and melanoma was to include under the subtopic "some of the genes affected by cytosine methylation in melanoma formation," additional genes that have been discussed which are present and found to be particularly hypermethylated in the formation of and late-onset stages of melanoma. While the two particular genes noted are important, I believe it would further the strength of the article overall to include other genes that are frequently found to be hypermethylated in melanoma to better improve the scope of the article itself. In addition, upon reading the review article, I believe it would be helpful to include a discussion on UV-exposure and its ties to melanogenesis through regulation by transcriptional factor MITF and G-protein coupled receptor (GPCR) activity in the formation of melanocytes and thus melanoma itself. While MITF is included briefly within the article, it is not suggested to be the primary regulatory factor involved in the formation of melanoma, as the review article suggests. The inclusion of this discussion into the article, potentially within the Lead section should function to improve the article's explanation of melanoma formation via epigenetic factors and gene regulation. Furthermore, while not a particularly pressing matter, I propose to make edits to the organization of the article itself, particularly by removing the in-text citations, such as "(Patino et al. 2008)" present in the subtopic "Role of cytosine methylation in melanoma" and rather hyperlinking the cited sources in order to clean up the article's presentation and make the article more well-finished.

Yes. You have a plan. I like it. See if there is a more recent review -- time to gather more resources. This is a pretty good article as it is and so it will take care to improve it. -- Dr. Atkinson

Article body

Some of the genes affected by cytosine hypermethylated in melanoma (edit)

INK4A

INK4A, also known as p16, is a tumor suppressor gene and is found to have hypermethylated promoter regions in 10- 20% of melanoma cells and is involved in 40- 87% of gene alterations in melanoma cases (Gonzalgo et al., 1997). This means that 10- 20% of the time there is an epigenetic change in the INK4A gene, and 40- 87% of the time there is a nucleotide mutation in the gene. INK4A is one of the genes that is both epigenetically and genomically altered. As a regularly functioning gene, INK4A is a tumor suppressor that functions to repress the formation of tumors. The hypermethylation of this gene can cause it to become inactivated (Straume et al., 2002). When INK4 is inactivated through hypermethylation, it causes an interruption of the CDK4 and CDK6 genes, which normally stop cell growth in the G1 phase of cell division. When this happens, there is no regulation in the cell and it grows quickly and becomes cancerous.

SYK

SYK is another gene that is affected by cytosine methylation during cancer progression. It is a gene that, when hypermethylated, loses function (Muthusamy et al., 2006). This gene is found in 30- 89% of melanoma cases (Dahl et al., 2007), and causes cells to grow quickly. This fast growth is important in the quick metastasis of melanoma cells, and when hypermethylated, the growth and spread of cells slow considerably (Hoeller et al., 2005). This is a controversial finding with inconclusive results, though. Some findings show that normally functioning SYK genes aids in tumor suppression, while other studies find that it is a transforming factor that facilitates cancer formation. Normally functioning, the SYK gene produces a non- receptor protein kinase enzyme that aids in differentiation, proliferation, and phagocytosis among many other important processes. SYK is found expressed in a variety of cells including fibroblasts, epithelial cells (where it controls cell division and acts as a tumor suppressor), hepatocytes, and neuronal cells (TORCIS Bioscience, 2014). Although SYK does not have any reported DNA modifications, the epigenetic changes still cause sufficient damage to cells. When SYK silencing is coupled with other alterations, both genetically and epigenetically, cancer can form.

RAR-β2 (RARB) (edit/addition)

RAR-β2 (RARB) is a tumor suppressor gene that is one of the most commonly hypermethylated genes and thus suppressed in malignant melanoma. In its functional state, this gene inhibits the proliferation of cancer cells by producing all-trans retinoic acid (ATRA). Studies have been conducted which display a direct correlation between the tumor-supressing activity of RARB and it product ATRA. Significantly, this hypermethylation of RAR-β2 (RARB) is found primarily in cells that are in the tumor-growth phase of melanoma, and it is proposed that RAR-β2 (RARB) may also be silenced, depending on the state of cancer progression, by the process of hypoacetylation, suggesting that silencing methods for this and other genes involved in cancer may differ in their mechanisms depending on their stage of melanoma.

References

[1] Sarkar, D., Leung, E. Y., Baguley, B. C., Finlay, G. J., & Askarian-Amiri, M. E. (2015). Epigenetic regulation in human melanoma: Past and future. Epigenetics, 10(2), 103–121. https://doi.org/10.1080/15592294.2014.1003746