Fragmentomics profiling and quantification of plasma Epstein-Barr virus DNA enhance prediction of future nasopharyngeal carcinoma
- PMID: 40054465
- DOI: 10.1016/j.ccell.2025.02.002
Fragmentomics profiling and quantification of plasma Epstein-Barr virus DNA enhance prediction of future nasopharyngeal carcinoma
Abstract
Fragmentomics analysis of plasma autosomal DNA has shown promise in cancer diagnostics. Here we evaluated the clinical utility of plasma Epstein-Barr virus (EBV) DNA fragmentomics analysis for nasopharyngeal carcinoma (NPC) screening. Among our prospective cohort of approximately 20,000 subjects that underwent two rounds of screening, we analyzed the first-round blood samples of subjects who tested positive for EBV DNA via polymerase chain reaction (PCR) (n = 558). We found that those who subsequently developed NPC in the second round exhibited a distinctive mononucleosomal size pattern, an NPC-associated end motif (specifically, a depletion of CC-motif) and aberrations in methylation identified through fragmentomics-based methylation analysis (FRAGMA). Subjects with these aberrant fragmentomics features and higher quantity of EBV DNA had a relative risk of 87.1 times greater for developing NPC in the second round compared to subjects tested negative for EBV DNA on PCR. These results demonstrate plasma DNA fragmentomics could predict future cancer risk.
Keywords: cancer screening; circulating tumor DNA; liquid biopsy; precision oncology; risk prediction.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests Y.M.D.L. holds equities in DRA, Take2, and Insighta. K.C.A.C. holds equities in DRA, Take2, Insighta, and Illumina. W.K.J.L and P.J. hold equities in Illumina. P.J. is a consultant to Take2. P.J. is a director of DRA and KingMed Future. W.K.J.L. is a director of DRA. E.P.H. receives speaker’s honoraria from Merck Sharp and Dohme (MSD) and Merck Serono and serves as a consultant or in the advisory board from MSD. B.B.Y.M. serves in the advisory board and receives speaker’s honorarium from Novartis, Bristol-Myers Squibb and MSD and receives research grant from Novartis. A.T.C.C. received research and travel grants from MSD, Pfizer, and Roche. Patent royalties are received from Grail, Illumina, LabCorp, DRA, Take2, Insighta, and Xcelom.