The Role of DNA Methylation in Cancer

Cancer is extremely prevalent in today’s society. We all have someone in our lives who has had, currently has, or has tragically passed away from this disease. Although knowledge about cancer and cancer research has expanded greatly, a great deal remains to be explored. One area of cancer research that has just recently begun to be investigated involves the concept of epigenetics. Epigenetics is the study of how behaviors or the environment impact the expression of genes. Contrary to genetics, epigenetics do not alter DNA sequences themselves but rather changes how the body reads those sequences (“What is Epigenetics?”, 2022). Epigenetics includes three main categories–DNA methylation, histone modification, and non-coding RNA. DNA methylation, in particular, is a very important area of epigenetics involving the transfer of a methyl group to the C5 position on a cytosine, causing silencing of a gene, leading to certain types of cancer (Saleem, et al., 2015). This paper will explore the role of DNA methylation in causing cancer as well as treatments being developed to combat the methylation of genes causing cancer. 

DNA methylation in cancer expression has two faces, the first of which is loss of methylation. Loss of methylation, found in studies measuring 5-methylcytosine content, is shown to be linked to carcinogenic, chromosomal breaks, and increased cancer expression in certain animals (Issa, 2007). DNA methylation plays a major role in cancer when it comes to hypermethylation. It is estimated that hundreds of genes are silenced leading to cancer expression. In particular, the silencing of tumor suppressor genes is a leading cause of cancer in many individuals. In addition, excessive DNA methylation was observed to be present in the promoter regions of such silenced genes in cancer patients (Issa, 2007). The role of DNA methylation in the silencing of genes and its effect on various genetic pathways highlights the fact that DNA methylation is a prominent factor in the formation of cancer. Thus, reducing the effects of hypermethylation as a form of cancer treatment is an important area of research that could massively reduce the prevalence of cancer in our community. 

Methods of determining sites of hypermethylation in certain cancer-linked genes can be very important in preventing and detecting cancer in some instances. One instance of cancer heavily impacted by DNA methylation patterns is breast cancer. Specifically, hypermethylation of the BRCA1 gene leads to de-expression of this gene, which raises the risk for certain breast and other cancers (“What is Epigenetics?”, 2022). Therefore, developing ways to detect and treat such hypermethylation patterns in breast and other cancer patients is crucial. In many instances, gene-specific methylation levels, methylation-specific PCR, and pyrosequencing are used to detect hypermethylation. However, several studies have shown epigenome-wide blood DNA methylation in breast cancer patients as disproportionately larger compared to those of control patients, especially in the ATM gene. Thus, another, potentially simpler, method of DNA hypermethylation detection using blood-based DNA methylation markers for breast cancer risk stratification is a possibility for the future (Tang, et al., 2012). 

Furthermore, virtually all colorectal cancers have aberrantly methylated genes. As Lao and Grady put it “The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications” (Lao and Grady, 2011). Such methods are becoming prominent methods for colon cancer screening, and serve as promising future areas of epigenetic hypermethylation detection for colon and other forms of cancer. 

In conclusion, DNA methylation and other forms of epigenetic influence on gene expression play a crucial role in cancer development. Therefore, methods for screening, detecting, and treating hypermethylation in cancer-linked genes are critical in increasing the survival rate of cancer patients. Overall, DNA methylation in cancer expression is still a fairly new area of cancer research that has much left to be explored. However, important discoveries have been made in terms of screening for methylation patterns in genes and treating hypermethylation in individuals with cancer, thus paving the way for new methods of aiding cancer patients.

References

Issa, Jean-Pierre J. (2007). DNA Methylation as a Therapeutic Target in Cancer. Clinical Cancer Research. https://aacrjournals.org/clincancerres/article/13/6/1634/195851/DNA-Methylation-as-a-Therapeutic-Target-in-Cancer. 

Lao, V. V., and Grady, W. M. (2011). Epigenetics and colorectal cancer. Nature reviews. Gastroenterology & hepatology. https://doi.org/10.1038/nrgastro.2011.173. 

Saleem, Mohammad. (2015). Epigenetic Therapy for Cancer. Review. https://www.researchgate.net/profile/Mohammad-Saleem/publication/273648245_Review-Epigenetic_therapy_for_cancer/links/55c1f21f08aeb5e0c584bb17/Review-Epigenetic-therapy-for-cancer.pdf. 

Tang, Q., et al. (2016). Blood-based DNA Methylation as Biomarker for Breast Cancer: a Systematic Review. Clinical epigenetics. https://doi.org/10.1186/s13148-016-0282-6. 

What is Epigenetics?. (2007). Genomics and Precision Health. https://www.cdc.gov/genomics/disease/epigenetics.htm#:~:text=Epigenetics%20is%20the%20study%20of,body%20reads%20a%20DNA%20sequence.