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PLoS One. 2017 Nov 16;12(11):e0188228. doi: 10.1371/journal.pone.0188228. eCollection 2017.

Spontaneous development of Epstein-Barr Virus associated human lymphomas in a prostate cancer xenograft program.

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Cancer Research Unit, Department of Biology, University of York, York, United Kingdom.
Department of Urology, St James University Hospital, Leeds, United Kingdom.
Leeds Institute of Cancer & Pathology, University of Leeds, Leeds, United Kingdom.
Department of Chemistry, University of York, York, United Kingdom.
Department of Urology, Castle Hill Hospital, Cottingham, United Kingdom.
Hull -York Medical School, University of York, York, United Kingdom.
Department of Pathology, Hull Royal Infirmary, Hull, United Kingdom.
Sheffield Institute for Nucleic Acids, Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom.
Department of Urology, Leiden University Medical School, Leiden, The Netherlands.


Prostate cancer research is hampered by the lack of in vivo preclinical models that accurately reflect patient tumour biology and the clinical heterogeneity of human prostate cancer. To overcome these limitations we propagated and characterised a new collection of patient-derived prostate cancer xenografts. Tumour fragments from 147 unsupervised, surgical prostate samples were implanted subcutaneously into immunodeficient Rag2-/-γC-/- mice within 24 hours of surgery. Histologic and molecular characterisation of xenografts was compared with patient characteristics, including androgen-deprivation therapy, and exome sequencing. Xenografts were established from 47 of 147 (32%) implanted primary prostate cancers. Only 14% passaged successfully resulting in 20 stable lines; derived from 20 independent patient samples. Surprisingly, only three of the 20 lines (15%) were confirmed as prostate cancer; one line comprised of mouse stroma, and 16 were verified as human donor-derived lymphoid neoplasms. PCR for Epstein-Barr Virus (EBV) nuclear antigen, together with exome sequencing revealed that the lymphomas were exclusively EBV-associated. Genomic analysis determined that 14 of the 16 EBV+ lines had unique monoclonal or oligoclonal immunoglobulin heavy chain gene rearrangements, confirming their B-cell origin. We conclude that the generation of xenografts from tumour fragments can commonly result in B-cell lymphoma from patients carrying latent EBV. We recommend routine screening, of primary outgrowths, for latent EBV to avoid this phenomenon.

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