HHV-8-unrelated primary effusion-like lymphoma associated with clonal loss of inherited chromosomally-integrated human herpesvirus 6A from the telomere of chromosome 19q

Zhang, E. et al. (2016) HHV-8-unrelated primary effusion-like lymphoma associated with clonal loss of inherited chromosomally-integrated human herpesvirus 6A from the telomere of chromosome 19q. Scientific Reports, 6, 22730. (doi:10.1038/srep22730) (PMID:26947392) (PMCID:PMC4779988)

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Abstract

Primary effusion lymphomas (PEL) are associated with human herpesvirus-8 (HHV-8) and usually occur in immunocompromised individuals. However, there are numerous reports of HHV-8-unrelated PEL-like lymphomas with unknown aetiology. Here we characterize an HHV-8-unrelated PEL-like lymphoma in an elderly woman who was negative for human immunodeficiency viruses 1 and 2, and hepatitis B and C. The woman was, however, a carrier of an inherited-chromosomally-integrated human herpesvirus-6A (iciHHV-6A) genome in one 19q telomere. The iciHHV-6A genome was complete in blood DNA, encoding a full set of proteincoding genes. Interestingly, the entire iciHHV-6A genome was absent from the HHV-8-unrelated- PEL-like lymphoma cells despite retention of both copies of chromosome 19. The somatic loss of the 19q-iciHHV-6A genome occurred very early during lymphoma development and we propose it occurred via telomere-loop formation and excision to release a circular viral genome that was subsequently lost. Whether release of the HHV-6A genome from the telomere contributed to lymphomagenesis, or was coincidental, remains unclear but this event may have deregulated the expression of HHV-6A or 19q genes or else disrupted telomere function. To establish the frequency and importance of iciHHV-6 loss from telomeres, the HHV-6 copy number should be assessed in tumours that arise in iciHHV-6 carriers.

Item Type:Articles
Additional Information:Funding from UK Medical Research Council [G0901657 to N.J.R.]; UK Medical Research Council [MC_UU_12014/3 to AJD]; Wellcome Trust Institutional Strategtic Support Fund [WT097828MF to NJR]; Conacyt, Mexico [to A.H.-B.].
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilkie, Dr Gavin and Bell, Dr Adam and Jarrett, Professor Ruth and Davison, Professor Andrew
Authors: Zhang, E., Cotton, V. E., Hidalgo-Bravo, A., Huang, Y., Bell, A. J., Jarrett, R. F., Wilkie, G. S., Davison, A. J., Nacheva, E. P., Sibert, R., Majid, A., Kelpanides, I., Dyer, M. J., and Royle, N. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Scientific Reports 6:22730
Publisher Policy:Reproduced under a creative commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656321Genomics of human cytomegalovirusAndrew DavisonMedical Research Council (MRC)MC_UU_12014/3MVLS III - CENTRE FOR VIRUS RESEARCH