New cfDNA/cfRNA panels target lymphoid subtyping
At the DAVA Whistler meeting, Stanford’s Ash Alizadeh presented EPIC‑Seq and RARE‑Seq workflows that use circulating cell‑free DNA and RNA to noninvasively subtype lymphoid cancers and assess risks like mantle cell progression. The platforms aim to distinguish origins of diffuse large B‑cell lymphoma and detect features relevant to prognosis. If robust, these liquid approaches could reduce dependence on repeat tissue sampling for subtyping in certain lymphoid cases. (x.com)
Cancer leaves scraps behind in the blood. Some are broken pieces of DNA, which is the long-term instruction manual, and some are broken pieces of RNA, which is the short-lived copy a cell makes when it is actively using a gene. (nature.com 1) (nature.com 2) Doctors already use tissue biopsies to sort lymphomas, but that usually means taking a piece of a swollen node or other involved tissue and running several lab tests on it. In diffuse large B-cell lymphoma, the most common aggressive lymphoma, those subtype calls can affect prognosis and treatment planning. (ashpublications.org) (sciencedirect.com) The problem is that a tissue biopsy is one snapshot from one place. If the sample is small, hard to reach, or low quality, extra tests like gene expression profiling can be delayed or never done. (ashpublications.org 1) (ashpublications.org 2) Stanford’s Ash Alizadeh has been building blood tests that try to read those tumor clues without another needle or surgery. At the DAVA Oncology Whistler Summit on Hematologic Malignancies, held April 7-11, 2026 in British Columbia, he presented two of them together for lymphoid cancers. (med.stanford.edu) (whistler.davaoncology.com) The first tool is called epigenetic expression inference from cell-free DNA sequencing, or EPIC-Seq. Instead of looking only for mutations, it studies how DNA fragments are chopped around gene start sites and uses that pattern to infer which genes the tumor is turning on. (nature.com) (med.stanford.edu) That matters because diffuse large B-cell lymphoma is not one disease wearing one name. EPIC-Seq was reported in Nature Biotechnology in 2022 after profiling 329 blood samples from 201 patients with cancer and 87 healthy adults, and the paper showed it could classify subtypes of diffuse large B-cell lymphoma from blood. (nature.com) The second tool is called random priming and affinity capture of cell-free RNA fragments for enrichment analysis by sequencing, or RARE-seq. It is built for cell-free RNA, which is much rarer and more fragile in blood than cell-free DNA, so the method enriches those fragments before sequencing them. (nature.com) In the 2025 Nature paper, RARE-seq was about 50-fold more sensitive than whole-transcriptome RNA sequencing for detecting tumor-derived cell-free RNA, with a reported limit of detection of 0.05%. The study profiled 437 plasma samples from 369 people and showed that blood RNA signals could identify cancer biology that mutation-only tests can miss. (nature.com) What Alizadeh appears to be doing now is applying those blood-based readouts to lymphoma questions that usually depend on tissue: cell of origin in diffuse large B-cell lymphoma, high-risk expression programs like the dark-zone signature, and progression signals in mantle cell lymphoma. That direction matches a 2025 American Society of Hematology abstract reporting EPIC-Seq for noninvasive classification and molecular subtyping across mature lymphoid neoplasms. (ashpublications.org 1) (ashpublications.org 2) If those results hold up in larger validation studies, the practical change is simple: a tube of blood could answer some of the subtype questions that now require enough viable tissue for RNA work, fluorescence in situ hybridization, or repeat biopsy. That would not replace pathology, but it could make real-time lymphoma subtyping faster when tissue is scarce or the disease changes between biopsies. (ashpublications.org) (ashpublications.org)
