DNA Methylation: An Emerging Biomarker for Cancer Research?

Genes can be turned on and off in a variety of ways as part of normal cellular functioning. One of the most common ways is through DNA methylation, in which methyl groups are temporarily affixed to the promoter regions of genes, deactivating the promoters and preventing the associated genes from being transcribed. When the genes deactivated with methylation or left active via a lack thereof are associated with cell-cycle progression, DNA repair, and other critical functions, it’s possible that an unusual methylation status can lead to carcinogenesis. Aberrant methylation patterns can be among the situations that turn normal cells into tumors and tumors metastatic.¹

Recent studies have shown that unusual methylation patterns are present across multiple cancer types and can affect a cancer’s progression and prognosis, making them relevant across oncological research.² DNA hypermethylation can directly silence tumor suppressor genes, a frequent and important step cancer development. For example, the SEPT9 gene encodes for the septin-9 protein, which is involved in cytokinesis during the cell division process and is also thought to be a tumor suppressor.³ Hypermethylation can also silence important transcription factors and DNA-repair mechanisms. Conversely, hypomethylation can lead to genomic instability and chromosomal rearrangements by keeping more of the genome than normal accessible to damaging factors. All of these events can promote the development of cancer.

It is known that these cancer-associated DNA methylation patterns can appear well before other signs of cancer, providing a very early biomarker that distinguishes tissue on the path to becoming cancerous from healthy tissue.² But additional research into the role of DNA methylation in carcinogenesis and the methods for detecting methylation patterns efficiently and accurately are critical for understanding the early progression of cancers.

Next-Generation Sequencing and DNA Methylation Analysis

Next-generation sequencing (NGS) is already established as a sensitive, specific methodology for studying multiple genomic regions at the same time, including their methylation status. It can even determine the entire methylome of a sample. Targeted next-generation sequencing with a curated group of markers is the most cost-effective strategy for any research lab, removing the issue of excess sequence data and simplifying analysis. NGS-based DNA methylation research in particular can be performed even with heterogenous or degraded samples, such as formalin-fixed paraffin-embedded (FFPE) tissues that have been stored for long periods.

The Ion AmpliSeq Methylation Panel for Cancer Research analyzes clinically relevant targets using the bisulfite method for identifying specific methylation patterns within a DNA sample. With low DNA input, the panel provides high accuracy, impressive ease of use, and rapid results that allow researchers to process large numbers of samples. For more information on this panel, follow the link above.

References

1. Watanabe, Y., & Maekawa, M. (2010). Methylation of DNA in cancer. Adv. Clin. Chem. 52:145–167.

2. Mancarella, D., & Plass, C. (2021). Epigenetic signatures in cancer: Proper controls, current challenges and the potential for clinical translation. Genome Med. 13(1):23.

3. Heyn, H., & Esteller, M. (2012). DNA methylation profiling in the clinic: Applications and challenges. Nat. Rev. Genet. 13(10):679–692.

For research use only. Not for use in diagnostic procedures.