BUFFALO, NY – May 19, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 9, 2025, titled “Analytical validation of a circulating tumor DNA assay using PhasED-Seq technology for detecting residual disease in B-cell malignancies.”
In this study, a team from Foresight Diagnostics led by first author Nina Klimova and corresponding author Laura Hyland validated a new DNA-based blood test designed to detect minimal residual disease (MRD) in patients with B-cell cancers. This assay uses a highly sensitive method called Phased Variant Enrichment and Detection Sequencing (PhasED-Seq) to find tiny fragments of tumor DNA in the blood. Its ultra-sensitive detection capabilities offer a powerful tool for early cancer detection, monitoring treatment response, and predicting cancer reappearance.
B-cell lymphomas, such as diffuse large B-cell lymphoma (DLBCL), are among the most prevalent blood cancers. Although many patients respond to initial treatment, up to 40% relapse. Standard monitoring methods such as imaging scans often miss low levels of cancer cells, creating a need for more precise tools. This study introduces a non-invasive blood test that improves the detection of MRD, a critical factor in guiding follow-up care and early intervention.
The test works by tracking unique groups of mutations known as phased variants in tumor DNA. These mutations are more specific to cancer and allow for highly accurate identification of tumor fragments in the bloodstream. The PhasED-Seq-based MRD assay was tested on three types of samples. First, blood plasma from healthy individuals was used to confirm the test does not give false positives. Second, researchers created controlled samples by mixing tumor DNA from lymphoma patients with healthy DNA to measure how sensitive and precise the test is. Finally, blood samples from patients with B-cell lymphoma were used to compare the new test to an existing method.
Across all sample types, the PhasED-Seq-based MRD assay demonstrated exceptional performance—capable of detecting fewer than one cancer DNA molecule per million normal DNA fragments. It also demonstrated a very low false positive rate and over 96% reproducibility across different laboratory conditions. Compared to an existing method, the new PhasED-Seq assay showed more than 90% agreement in positive results and nearly 78% agreement in negative results. In cases where the tests disagreed, the new method aligned more closely with actual clinical outcomes, including whether patients relapsed or stayed in remission.
“The background error rate of the PhasED-Seq-based MRD assay was 1.95E-08, or 1.95 mutant molecules in 100 million informative molecules.”
The findings support the use of PhasED-Seq-based MRD assays in routine clinical practice. It could be especially useful for identifying patients who need additional treatment even when imaging results appear normal. This aligns with updated clinical guidelines that encourage the use of blood-based DNA tests to supplement traditional scans in lymphoma care.
This study offers strong evidence that the PhasED-Seq-based MRD assay is a precise, reliable, and clinically relevant tool. By detecting signs of cancer earlier and more accurately, it may help clinicians tailor treatments to individual patients and improve long-term outcomes in B-cell malignancies.
DOI - https://doi.org/10.18632/oncotarget.28719
Correspondence to - Laura Hyland - laura.hyland@foresight-dx.com
Video short - https://www.youtube.com/watch?v=8hdh3G5zvlc
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