title: Evaluation of the risk of lymphomagenesis in xenografts by the PCR-based detection of EBV BamHI W region in patient cancer specimens.
abstract: Establishment of patient-derived tumor xenografts (PDXs) is hampered by lymphomagenesis mostly caused by the latently-infected Epstein-Barr virus (EBV) contained in patient cancer tissues. However, the character of patient tissues that result in lymphomagenesis after xenotransplantation is not elucidated. In this study, we analyzed the patient colorectal cancer (CRC) tissues and the PDXs established by their xenotransplantation. We found that 2 of 9 (22%) PDX tumors were EBV-associated human diffuse large B cell lymphoma which was formed by clonal proliferation of human B-cell lymphocytes, were strongly positive for EBER-ISH, and were classified as type III latency. Expression of EBV genes and RNAs, such as EBNAs, LMP1, EBER and EBV-associated microRNAs in patient CRC tissues were unlikely to be associated with lymphomagenesis in PDXs. In contrast, the positive PCR-based amplification of BamHI W region, a major internal repeat in EBV genome, in the patient CRC tissues was correlated with lymphomagenesis in PDXs. These results suggest that the detection of the EBV BamHI W region in the patient surgical specimens will be an effective way to predict the risk of lymphomagenesis in PDXs before xenotransplantation.
authors.affiliation: Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.|Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Mukohyama
authors.affiliation: Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Iwakiri
authors.affiliation: Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.affiliation: Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.|Cancer Center, Kobe University Hospital, Kobe, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Mukohara
authors.affiliation: Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.|Cancer Center, Kobe University Hospital, Kobe, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
authors.affiliation: Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.affiliation: Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.|Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Shimono
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D063646:Carcinogenesis; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004279:DNA, Viral / Q000235:genetics; D015245:Deoxyribonuclease BamHI / Q000235:genetics*; D020031:Epstein-Barr Virus Infections / Q000473:pathology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000821:virology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D012306:Risk; D014763:Viral Matrix Proteins / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D007143:Immunoglobulin Heavy Chains; D014763:Viral Matrix Proteins; D015245:Deoxyribonuclease BamHI
keywords: BamHI W region; Epstein-Barr virus; colorectal cancer; lymphomagenesis; patient-derived tumor xenograft