Achyut Saroj, Founder, Consultant, and Author at AwareOnc, KOL Engagement and Medical Affairs Liaison at Tatva Health, shared a post on LinkedIn:
” ‘How Methylation Is Rewriting the Rules of Liquid Biopsy in Solid Tumors‘
For years, the performance of liquid biopsies in solid tumors has been limited by tumor biology.
Many cancers do not shed enough ctDNA to be reliably detected using mutation-only approaches, limiting MRD assessment, surveillance, and early detection.
That paradigm is changing.
Advances in cfDNA methylation profiling are redefining what’s detectable, particularly in low-shedding and hard-to-monitor tumors.
Unlike variant-based assays, methylation assays analyze genome-wide epigenetic patterns, signals that are more abundant, tissue-specific, and often detectable even when the ctDNA fraction is extremely low.
We’re already seeing this shift across multiple solid tumor settings:
- Helio Liver Dx – methylation-based blood test improving detection of hepatocellular carcinoma (HCC) in cirrhotic patients.
- GRAIL Galleri – multi-cancer early detection using cfDNA methylation patterns across >50 cancer types.
- Guardant Reveal – CRC surveillance combining methylation with mutation detection in a plasma-only assay.
- Northstar Response / Natera Latitude MRD/ Haystack MRD – methylation-forward strategies advancing MRD detection in low-shedding breast and other solid tumors.
Emerging tumor-naive methylation and fragmentomics platforms – under active validation in pancreatic, renal cell, and upper GI malignancies.
As clinical evidence expands, methylation is emerging as a critical key to unlocking the potential of liquid biopsy, extending sensitivity beyond “high shedders” and bringing molecular detection to tumors that were previously invisible in blood.
Low shedding no longer has to mean low insight.
How do you view methylation as a driver in liquid biopsy-based diagnostics?”
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