DNA methylation patterns may be less expensive way to identify early or precancer

A new blood test developed by UCLA researchers can detect multiple cancers and other diseases from a single draw at an estimated cost of less than $20 per sample, according to a UCLA press release and a study published April 6 in the Proceedings of the National Academy of Sciences (PNAS).

The test, called MethylScan, analyzes chemical modifications on cell-free DNA circulating in the bloodstream rather than hunting for rare tumor mutations, an approach the researchers say dramatically reduces sequencing costs while maintaining clinically meaningful sensitivity across cancer types and stages.

In a study of 1,061 individuals, MethylScan identified cancers of the liver, lung, ovary and stomach with 63% sensitivity across all stages at 98% specificity. For early-stage cancers, sensitivity was approximately 55%. Among high-risk individuals with liver cirrhosis or hepatitis B, the test detected nearly 80% of liver cancers at just over 90% specificity.

"Early detection is crucial. Survival rates are far higher when cancers are caught before they spread," said Jasmine Zhou, Ph.D., the study's senior author, a professor of pathology and laboratory medicine and investigator at the UCLA Health Jonsson Comprehensive Cancer Center.

The approach marks a departure from existing multicancer early detection tests, which can cost upwards of $950 per screen. Current commercially available assays from companies like Grail and Guardant Health rely on deep sequencing to detect faint tumor signals in a sea of normal cell-free DNA, a technically demanding process that drives up per-sample costs.

MethylScan sidesteps that bottleneck by using specialized enzymes to selectively remove unmethylated DNA fragments, which predominantly originate from blood cells and account for 80% to 90% of circulating cell-free DNA. What remains is an enriched pool of methylated fragments from solid organs, including potentially diseased tissue. A custom genome-wide hybridization panel then captures these fragments for sequencing.

The result is an effective sequencing depth only requiring a fraction of what comparable assays require in terms of data.

"DNA methylation reflects the health status of a tissue. It's a very informative signal," said Wenyuan Li, Ph.D., a professor of pathology and laboratory medicine at UCLA and co-corresponding author of the study, said in the press release.

“Unlike an individual’s genome, which remains largely stable across tissues and over time (except for rare somatic mutations), the DNA methylome is tissue-specific and dynamically changes with the tissue’s disease status,“ Li and his colleagues wrote in PNAS.

They continued, saying that nearly all diseases leave a signature in DNA methylation in two important ways: the aberrant DNA methylation patterns and an increase the rate of cell death that results in elevated levels of the DNA from the impacted tissues in the blood. “Because each tissue type has a distinct DNA methylation pattern, it is possible to trace the tissue of origin of cfDNA and infer the increased death of specific cell types,” they wrote in PNAS.

Beyond cancer detection, MethylScan demonstrated the ability to identify the tissue of origin of abnormal signals and to distinguish among different liver disease types, including viral hepatitis and metabolic-associated liver disease, with roughly 85% accuracy. The researchers described the platform as a potential "health radar" capable of flagging organ-level stress before clinical symptoms emerge.

The study's multi-disease capability could carry significant implications for payer strategy and population health screening. A sub-$20 per-sample cost point, if validated in larger prospective trials, would represent a substantial reduction in the economic barrier to deploying liquid biopsy at scale, particularly for cancers that currently lack routine screening recommendations, such as ovarian and stomach malignancies.

The research was funded in part by grants from the National Cancer Institute.

Zhou said larger prospective studies will be needed to confirm MethylScan's real-world screening performance but described the work as progress toward a long-sought goal in precision diagnostics.

"This study demonstrates that blood-based methylation profiling can deliver clinically meaningful information across multiple diseases," she said.