Quantitative off-target detection of Epstein-Barr virus–derived DNA in routine molecular profiling of hematopoietic neoplasms by panel-based hybrid-capture next-generation sequencing Journal Article


Authors: Petrova-Drus, K.; Quesada, A. E.; Bowman, A. S.; Ptashkin, R.; Yao, J.; Arcila, M. E.; Ho, C.; Moung, C.; Regalado, J.; Benayed, R.; Benhamida, J. K.; Galera, P. K.; Dogan, A.; Vanderbilt, C.
Article Title: Quantitative off-target detection of Epstein-Barr virus–derived DNA in routine molecular profiling of hematopoietic neoplasms by panel-based hybrid-capture next-generation sequencing
Abstract: Epstein-Barr virus (EBV) is associated with hematologic and solid tumors. We utilized a hybridization capture–based next-generation sequencing (NGS) platform targeting 400 genes associated with hematological malignancies to detect and quantify nontargeted viral-derived EBV reads that aligned to the EBV reference contig (NC_007605). We evaluated 5234 samples from 3636 unique patients with hematological neoplasms and found that 100 samples (1.9%) in 93 unique patients had ≥6 EBV reads (range, 6 to 32,325; mean, 827.5; median, 54). Most (n = 73, 73%) represented known EBV-associated conditions, and the most common was post-transplant lymphoproliferative disorders (n = 21, 29%). Documented EBV viremia was found in 4 of 27 samples with a moderate quantity of EBV reads and conditions not known to be EBV associated, whereas suspected viremia or low-level activation was likely in the remaining 23 samples. A good correlation (Spearman r = 0.8; 95% CI, 0.74–0.85) was found between EBV reads by NGS and systematic semiquantitative EBV-encoded RNA in situ hybridization in 162 available samples, particularly at greater EBV involvement. An optimal threshold for significant morphologic EBV involvement was found to be ≥10 reads by the receiver operating characteristic analysis (area under the curve, 0.990; 95% CI, 0.9974%–1.000%). Thus, in addition to mutational analysis, hybrid-capture–based NGS panels can detect and quantitate off-target EBV-derived viral DNA, which correlates well with morphology. © 2022 Association for Molecular Pathology and American Society for Investigative Pathology
Journal Title: Journal of Molecular Diagnostics
Volume: 24
Issue: 1
ISSN: 1525-1578
Publisher: Elsevier Science, Inc.  
Date Published: 2022-01-01
Start Page: 69
End Page: 78
Language: English
DOI: 10.1016/j.jmoldx.2021.10.009
PUBMED: 34801704
PROVIDER: scopus
PMCID: PMC8802759
DOI/URL:
Notes: Article -- Export Date: 1 February 2022 -- Source: Scopus
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MSK Authors
  1. Jinjuan Yao
    45 Yao
  2. Christine Gi-Yun Moung
    19 Moung
  3. Maria Eugenia Arcila
    559 Arcila
  4. Ahmet Dogan
    331 Dogan
  5. Rym Benayed
    170 Benayed
  6. Caleb   Ho
    66 Ho
  7. Anita S Bowman
    28 Bowman
  8. Pallavi Kanwar Galera
    8 Galera