title: Patient-derived xenografts of gastrointestinal cancers are susceptible to rapid and delayed B-lymphoproliferation.
abstract: Patient-derived cancer xenografts (PDX) are widely used to identify and evaluate novel therapeutic targets, and to test therapeutic approaches in preclinical mouse avatar trials. Despite their widespread use, potential caveats of PDX models remain considerably underappreciated. Here, we demonstrate that EBV-associated B-lymphoproliferations frequently develop following xenotransplantation of human colorectal and pancreatic carcinomas in highly immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice (18/47 and 4/37 mice, respectively), and in derived cell cultures in vitro. Strikingly, even PDX with carcinoma histology can host scarce EBV-infected B-lymphocytes that can fully overgrow carcinoma cells during serial passaging in vitro and in vivo. As serial xenografting is crucial to expand primary tumor tissue for biobanks and cohorts for preclinical mouse avatar trials, the emerging dominance of B-lymphoproliferations in serial PDX represents a serious confounding factor in these models. Consequently, repeated phenotypic assessments of serial PDX are mandatory at each expansion step to verify "bona fide" carcinoma xenografts.
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Dieter
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Klara M
authors.initials: KM
authors.lastname: Giessler
authors.affiliation: Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Kriegsmann
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Taronish D
authors.initials: TD
authors.lastname: Dubash
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Lino
authors.initials: L
authors.lastname: Möhrmann
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Erik R
authors.initials: ER
authors.lastname: Schulz
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Siegl
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weber
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Strakerjahn
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Ava
authors.initials: A
authors.lastname: Oberlack
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heger
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jianpeng
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Hartinger
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Oppel
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hoffmann
authors.affiliation: Department of Applied Bioinformatics, NCT Heidelberg and DKFZ, Heidelberg, Germany.
authors.forename: Nati
authors.initials: N
authors.lastname: Ha
authors.affiliation: Department of Applied Bioinformatics, NCT Heidelberg and DKFZ, Heidelberg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brors
authors.affiliation: Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Lasitschka
authors.affiliation: Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Alexis
authors.initials: A
authors.lastname: Ulrich
authors.affiliation: Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Strobel
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|Heidelberg Center for Personalized Oncology, DKFZ-HIPO, DKFZ, Heidelberg, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.affiliation: Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.|Institute of Pathology, Technische Universität München (TUM), Munich, Germany.|DKTK, Munich, Germany.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Medical Oncology, NCT Heidelberg, Heidelberg, Germany.|Department of Internal Medicine VI, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: K Roland
authors.initials: KR
authors.lastname: Ehrenberg
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Glimm
authors.affiliation: Department of Translational Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Ball
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D001402:B-Lymphocytes / Q000473:pathology / Q000637:transplantation* / Q000821:virology; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000473:pathology* / Q000821:virology; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology* / Q000821:virology; D016895:Culture Media, Serum-Free; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000473:pathology*; D064593:Heterografts / Q000276:immunology / Q000473:pathology; D006801:Humans; D016867:Immunocompromised Host; D017493:Leukocyte Common Antigens / Q000032:analysis; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D009928:Organ Specificity; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology* / Q000821:virology; D018874:Spheroids, Cellular; D013370:Subrenal Capsule Assay / Q000379:methods
chemical_list: D000951:Antigens, Neoplasm; D016895:Culture Media, Serum-Free; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
keywords: colorectal cancer; lymphoproliferation; pancreatic cancer; patient-derived xenograft