Methylation analysis of plasma DNA informs etiologies of Epstein-Barr virus-associated diseases

W. K. Jacky Lam, Peiyong Jiang, K. C. Allen Chan, Wenlei Peng, Huimin Shang, Macy M. S. Heung, Suk Hang Cheng, Haiqiang Zhang, O. Y. Olivia Tse, Radha Raghupathy, Brigette B. Y. Ma, Edwin P. Hui, Anthony T. C. Chan, John K. S. Woo, Rossa W. K. Chiu and Y. M. Dennis Lo ()
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W. K. Jacky Lam: The Chinese University of Hong Kong, Shatin, New Territories
Peiyong Jiang: The Chinese University of Hong Kong, Shatin, New Territories
K. C. Allen Chan: The Chinese University of Hong Kong, Shatin, New Territories
Wenlei Peng: The Chinese University of Hong Kong, Shatin, New Territories
Huimin Shang: The Chinese University of Hong Kong, Shatin, New Territories
Macy M. S. Heung: The Chinese University of Hong Kong, Shatin, New Territories
Suk Hang Cheng: The Chinese University of Hong Kong, Shatin, New Territories
Haiqiang Zhang: The Chinese University of Hong Kong, Shatin, New Territories
O. Y. Olivia Tse: The Chinese University of Hong Kong, Shatin, New Territories
Radha Raghupathy: The Chinese University of Hong Kong, Shatin, New Territories
Brigette B. Y. Ma: The Chinese University of Hong Kong, Shatin, New Territories
Edwin P. Hui: The Chinese University of Hong Kong, Shatin, New Territories
Anthony T. C. Chan: The Chinese University of Hong Kong, Shatin, New Territories
John K. S. Woo: The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories
Rossa W. K. Chiu: The Chinese University of Hong Kong, Shatin, New Territories
Y. M. Dennis Lo: The Chinese University of Hong Kong, Shatin, New Territories

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Epstein-Barr virus (EBV) is associated with a number of diseases, including malignancies. Currently, it is not known whether patients with different EBV-associated diseases have different methylation profiles of circulating EBV DNA. Through whole-genome methylation analysis of plasma samples from patients with nasopharyngeal carcinoma (NPC), EBV-associated lymphoma and infectious mononucleosis, we demonstrate that EBV DNA methylation profiles exhibit a disease-associated pattern. This observation implies a significant potential for the development of methylation analysis of plasma EBV DNA for NPC diagnostics. We further analyse the plasma EBV DNA methylome of NPC and non-NPC subjects from a prospective screening cohort. Plasma EBV DNA fragments demonstrate differential methylation patterns between NPC and non-NPC subjects. Combining such differential methylation patterns with the fractional concentration (count) and size of plasma EBV DNA, population screening of NPC is performed with an improved positive predictive value of 35.1%, compared to a count- and size-based only protocol.

Date: 2019
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DOI: 10.1038/s41467-019-11226-5

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