Journal Article DKFZ-2017-00078

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Patient-derived xenografts of gastrointestinal cancers are susceptible to rapid and delayed B-lymphoproliferation.

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2017
Wiley-Liss Bognor Regis

International journal of cancer 140(6), 1356 - 1363 () [10.1002/ijc.30561]
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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-Prkdc(scid) Il2rg(tm1Wjl) /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.

Classification:

Contributing Institute(s):
  1. Geschäftsstelle (G010)
  2. Translationale Onkologie (G100)
  3. Angewandte Bioinformatik (G200)
  4. Epidemiologisches Krebsregister Baden-Württemberg (M110)
  5. DKTK Heidelberg (L101)
Research Program(s):
  1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2017
Database coverage:
Medline ; BIOSIS Previews ; Current Contents - Life Sciences ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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 Record created 2017-02-09, last modified 2024-02-28



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