Evaluation of the risk of lymphomagenesis in xenografts by the PCR-based detection of EBV BamHI W region in patient cancer specimens
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Junko Mukohyama1,2, Dai Iwakiri3, Yoh Zen4, Toru Mukohara5,6, Hironobu Minami5,6, Yoshihiro Kakeji2, Yohei Shimono1,5
1Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, Kobe, Japan
2Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
3Division of Clinical Virology, Kobe University Graduate School of Medicine, Kobe, Japan
4Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
5Division of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan
6Cancer Center, Kobe University Hospital, Kobe, Japan
Yohei Shimono, email: firstname.lastname@example.org
Keywords: patient-derived tumor xenograft, lymphomagenesis, Epstein-Barr virus, colorectal cancer, BamHI W region
Received: April 26, 2016 Accepted: June 13, 2016 Published: June 29, 2016
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.
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