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An Epigenetic Liquid Biopsy

by | Sep 5, 2023 | Medical Device & Diagnostic


Biopsy. The word may still evoke thoughts of painful cutting and poking, but we’ve come a long way. Liquid biopsies have been a hot topic in cancer diagnostics for a while now. They rely on the fact that tumors shed DNA and cells into bodily fluids like blood, urine, or saliva. This makes them a far more attractive alternative to traditional tissue biopsies. But there was always a catch: the cost. Early versions relied on expensive, lab-based technologies like DNA sequencing.

Enter 2023, and the landscape has changed dramatically. The focus has shifted to epigenetic markers, which are proving to be more sensitive and universal markers for evidence of cancer after curative intent treatment1. Companies like Guardant Health have even combined somatic mutations, DNA methylation, and fragmentomics into their LUNAR panel, which is in clinical trials for both primary detection and minimal residual disease (MRD) of early-stage colorectal cancer.


Epigenetic modifications are changes to DNA that don’t alter the actual gene sequence themselves, like mutations. Instead, they are chemical modifications to the DNA. These alterations typically affect gene expression, that is, how often a gene gets read by the cell.

One of the most common types of epigenetic modifications is methylation—the addition of a methyl (CH3) group to cytosine (C) nucleotides.

DNA methylation

The end result: methylation reduces or even blocks gene expression. Areas of the genome with methyl groups attached to them are referred to as methylated. DNA methylation is a normal part of cellular development. However, variations in the “normal” methylation pattern are associated with the disease.


Back in 2018, researchers were excited about a “methylscape” that seemed common to most cancers. Fast forward to 2023, and the field has evolved. Epigenetic-based MRD assays are preferable at treatment onset, as epigenetic changes are typically more widespread and likely to be shared among a greater number of cancers than somatic mutations. Companies like MethylGene are undertaking clinical trials that utilize DNA methylation sequencing of circulating tumor DNA (ctDNA) for MRD detection.


Remember the gold nanoparticle test from 2018? Well, the field has moved beyond that. DNA methylation-based PCR tests currently offer the most cost-effective solution within this niche. These tests are not just about detecting cancer; they’re about understanding its intricate epigenetic landscape, which can inform subsequent treatment.


The new tests are shaping up to be everything we hoped for and more. They promise to be universal, inexpensive, and fast. With the advent of enzymatic methylation conversion and targeted sequencing approaches combining DNA methylation, fragmentomics, and machine learning, the future looks bright.


Researchers are working tirelessly to bring these new tests into clinical practice. The promise of MRD assays that incorporate epigenetics with somatic mutation testing is being realized. Only time will tell, but these innovative new tests could dramatically change the cancer diagnostics landscape.


As we step further into 2023, the future of cancer diagnostics is looking increasingly promising. The advancements in epigenetic liquid biopsies are not just incremental; they are revolutionary. From the integration of somatic mutations, DNA methylation, and fragmentomics in tests like the LUNAR panel to the cost-effective and rapid DNA methylation-based PCR tests, we are on the cusp of a new era. These tests are not just about detecting cancer; they are about understanding it at a molecular level, which could significantly impact treatment plans and outcomes. While there is still work to be done, the progress made is a beacon of hope for both clinicians and patients. The future is not just on the horizon; it’s already here.


1. What is an Epigenetic Liquid Biopsy?

An epigenetic liquid biopsy is a type of test that detects cancer by examining epigenetic markers like DNA methylation in bodily fluids such as blood, urine, or saliva. Liquid biopsies, which require tissue samples, are less invasive than traditional biopsies.

2. How is it different from traditional biopsies?

Traditional biopsies often require surgical procedures to obtain tissue samples, which can be painful and carry risks. Liquid biopsies are less invasive, requiring only a sample of bodily fluid.

3. What are the advantages of using epigenetic markers?

Epigenetic markers like DNA methylation are more sensitive and universal, making them excellent candidates for detecting various cancers at different stages.

4. What is MRD?

Minimal Residual Disease (MRD) is the small number of cancer cells that may remain after treatment and could lead to relapse. Epigenetic liquid biopsies are increasingly being used for MRD detection.

5. How reliable are these new tests?

Companies like Guardant Health and MethylGene are in clinical trials to establish the reliability of these new tests. Early results are promising, showing high sensitivity and specificity.

6. How soon can we expect these tests to be widely available?

While it’s difficult to give a specific timeline, the rapid advancements and ongoing clinical trials suggest that these tests could become a standard part of cancer diagnostics in the near future.

7. Are these tests expensive?

One of the major advantages of the new generation of epigenetic liquid biopsies is their cost-effectiveness, especially when compared to the older, lab-based technologies.

8. Can these tests replace traditional biopsies?

While incredibly promising, epigenetic liquid biopsies are not yet a replacement for traditional biopsies but can serve as a complementary diagnostic tool.

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Author: Emily Burke, PhD
Editor: Sarah Van Tiems, MS
Scientific Review: Tahir Hayat, MS


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