Methylation Analysis for Cancer Diagnosis and Monitoring
What role does DNA methylation play in cancer?
DNA methylation, the addition of a methyl group to cytosine bases in DNA, is one of the most well-studied epigenetic modifications. In cancer, methylation patterns become disrupted: tumor suppressor genes often become hypermethylated and silenced, while oncogenes may lose methylation, leading to uncontrolled cell growth.
In addition, cells in our bodies, including cancer cells, release DNA fragments -- called cell-free DNA, or cfDNA -- into our blood. These cfDNA fragments have methyl molecules attached to them in methylation patterns to turn genes (sections of the DNA) on and off. The methylation patterns are different between cancer cells and healthy cells, so cfDNA methylation can be used as a cancer “fingerprint”, enabling distinction between cells from different organs. These methylation patterns predict the cancer signal origin, potentially enabling a pan-cancer diagnostic that can both identify and distinguish cancers from different tissues.
Clinical applications for epigenetics: From tissue to liquid biopsy
DNA methylation biomarkers are now being integrated into cutting-edge diagnostic and prognostic assays across oncology. Cancer often hides, with symptoms not appearing until later stages. The earlier that cancer is diagnosed, the greater the chance of successful treatment and survival.
Methylation markers for early cancer detection and screening
Methylation markers such as MGMT1, SEPT9, SHOX2, and RASSF1A are used to detect glioblastoma, colorectal, lung, and breast cancers at their earliest stages. These methylation signatures can reveal tumor presence long before anatomical changes appear on imaging.
A leading example is Epi proColon® (Epigenomics AG), the first FDA-approved blood-based colorectal cancer screening test, which detects methylated SEPT9 DNA in plasma.
Methylation profiling in non-invasive liquid biopsy
Cell-free DNA (cfDNA) in blood or urine carries the same methylation signatures as tumor tissue, enabling minimally invasive early cancer detection and recurrence monitoring. This has given rise to the new era of liquid biopsies that enable real-time insights into tumor dynamics.
One of the most advanced examples is Galleri® (Grail), a multi-cancer early detection (MCED) test that profiles cfDNA methylation patterns from a single blood sample to detect signals from multiple cancer types, often before clinical symptoms appear.
Treatment stratification and MRD tracking from methylation analysis
Dynamic changes in methylation profiles provide insights into treatment response, tumor heterogeneity, and residual disease, offering clinicians real-time molecular guidance.
For instance, Guardant Reveal™ (Guardant Health) integrates cfDNA methylation analysis with mutation tracking to identify MRD in colorectal and lung cancer patients.
Why bisulfite conversion matters for cancer epigenetics
The gold standard for DNA methylation analysis is largely built upon bisulfite conversion, a chemical process that differentiates methylated from unmethylated cytosines. Bisulfite conversion offers more robust, efficient, and consistent performance across diverse DNA sequence contexts compared to other methylation analysis methods. The result is high analytical accuracy and streamlined workflows that have made bisulfite conversion foundational to most methylation assays.
However, conventional bisulfite treatment is chemically harsh, it can fragment DNA and significantly reduce yield. These challenges are especially pronounced when working with low-input samples, such as cfDNA from liquid biopsies, where DNA integrity and recovery are critical for sensitive downstream analysis.
How Ellis Bio’s next-generation bisulfite technology solves for DNA fragmentation and delivers advanced insights in cancer epigenetics
SuperMethyl™ Max Kit – Maximum Accuracy and Recovery
- Ultra-Mild Conversion: preserves DNA integrity while achieving exceptionally high 99.8% C-to-T conversion ratios with near-zero false positives.
- High Yield and Precision: Enables accurate methylation analysis from as low as 100 pg input DNA, producing high-yield libraries.
- Fragmentomics Preservation: Ultra-mild bisulfite minimizes DNA damage and preserves cfDNA fragment size distribution, ensuring reliable integration of methylation and fragmentomic data.
- Best For: Projects that require maximum sensitivity methylation data using low-input cfDNA and FFPE-derived samples, such as early cancer detection or MRD monitoring.
SuperMethyl™ Fast Kit – Simple Workflow and Rapid Turnaround
- Ultra-Fast Workflow: Completes bisulfite conversion in 7 minutes, enabling ultra-fast turnaround and high-throughput processing.
- High Accuracy: Maintains excellent C-to-T conversion ratios and minimal false positives, ensuring reliable results in less time.
- Best For: Clinical or research workflows that demand speed, scalability, and consistent performance across diverse sample types.
Our technology empowers clinicians and researchers to unlock the full potential of DNA methylation biomarkers, driving progress in early cancer detection, liquid biopsy development, and precision oncology.
References
- American Cancer Society. The cancer atlas. [Internet] Early detection. https://canceratlas.cancer.org/taking-action/early-detection/
- If cancer is detected early, it is more amenable to curative treatment. Cancer treatment is based on the stage of the cancer (CDC, https://www.cdc.gov/cancer/survivors/patients/treatments.htm).
- NORC at the University of Chicago Cancer Detection Tool: https://cancerdetection.norc.org/
- Klein EA, Richards D, Cohn A, et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann Oncol. 2021;32(9):1167-77. DOI: https://doi.org/10.1016/j.annonc.2021.05.806
- Schrag D, Beer TM, McDonnell CH, et al. Blood-based tests for multi-cancer early detection (PATHFINDER): a prospective cohort study. Lancet. 2023;402:1251-1260. doi: 10.1016/S0140-6736(23)01700-2