title: HHV-8-unrelated primary effusion-like lymphoma associated with clonal loss of inherited chromosomally-integrated human herpesvirus-6A from the telomere of chromosome 19q.
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 protein-coding 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.
authors.affiliation: Department of Genetics, University of Leicester, Leicester, LE1 7RH, UK.
authors.forename: Enjie
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Department of Genetics, University of Leicester, Leicester, LE1 7RH, UK.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Cotton
authors.affiliation: Department of Genetics, University of Leicester, Leicester, LE1 7RH, UK.
authors.forename: Alberto
authors.initials: A
authors.lastname: Hidalgo-Bravo
authors.affiliation: Department of Genetics, University of Leicester, Leicester, LE1 7RH, UK.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: MRC - University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Bell
authors.affiliation: MRC - University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Jarrett
authors.affiliation: MRC - University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Wilkie
authors.affiliation: MRC - University of Glasgow Centre for Virus Research, Glasgow G61 1QH, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Davison
authors.affiliation: Cytogenetics Laboratory, Royal Free London NHS Foundation Trust, London, NW3 2PF, UK.
authors.forename: Ellie P
authors.initials: EP
authors.lastname: Nacheva
authors.affiliation: Institute of Human Genetics, Christian-Albrechts-University Kiel &University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 24, D-24105 Kiel, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Ernest and Helen Scott Haematological Research Institute, Department of Cancer Studies, University of Leicester, Leicester, LE1 7RH, UK.
authors.forename: Aneela
authors.initials: A
authors.lastname: Majid
authors.affiliation: Ernest and Helen Scott Haematological Research Institute, Department of Cancer Studies, University of Leicester, Leicester, LE1 7RH, UK.
authors.forename: Inga
authors.initials: I
authors.lastname: Kelpanides
authors.affiliation: Ernest and Helen Scott Haematological Research Institute, Department of Cancer Studies, University of Leicester, Leicester, LE1 7RH, UK.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jayne
authors.affiliation: Ernest and Helen Scott Haematological Research Institute, Department of Cancer Studies, University of Leicester, Leicester, LE1 7RH, UK.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Dyer
authors.affiliation: Department of Genetics, University of Leicester, Leicester, LE1 7RH, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Royle
mesh_terms: D000368:Aged; D002888:Chromosomes, Human, Pair 19; D005260:Female; D015654:Herpesvirus 6, Human / Q000235:genetics*; D006801:Humans; D054685:Lymphoma, Primary Effusion / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D008297:Male; D011533:Proviruses / Q000235:genetics*; D019349:Roseolovirus Infections / Q000150:complications*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D016615:Telomere; D016662:Virus Integration