CpG methylation in cell-free Epstein-Barr virus DNA in patients with EBV-Hodgkin lymphoma
Meir Shamay, Jennifer A. Kanakry, John Soon Wah Low, Netanel A. Horowitz, Guy Journo, Anuj Ahuja, Yonatan Eran, Elinor Barzilai, Eldad J. Dann, Jennifer Stone, Wan Lu Woo, Wen‐Son Hsieh, Rena R. Xian, Richard F. Ambinder
Abstract
Epstein-Barr virus (EBV) is associated with a variety of tumors and nonmalignant conditions. Latent EBV genomes in cells, including tumor cells, are often CpG methylated, whereas virion DNA is not CpG methylated. We demonstrate that methyl CpG binding magnetic beads can be used to fractionate among sources of EBV DNA (DNA extracted from laboratory-purified virions vs DNA extracted from latently infected cell lines). We then applied the technique to plasma specimens and showed that this technique can distinguish EBV DNA from patients with EBV-associated tumors (nasopharyngeal carcinoma, Hodgkin lymphoma) and viral DNA from patients without EBV-associated tumors, including immunocompromised patients and patients with EBV(-) Hodgkin lymphoma.