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Neuroblastoma Patient-Derived Orthotopic Xenografts Retain Metastatic Patterns and Geno- and Phenotypes of Patient Tumours.

Braekeveldt, Noémie LU ; Wigerup, Caroline LU ; Gisselsson Nord, David LU ; Mohlin, Sofie LU ; Merselius, My; Beckman, Siv LU ; Jonson, Tord LU ; Börjesson, Anna LU ; Backman, Torbjörn LU and Tadeo, Irene, et al. (2015) In International Journal of Cancer 136(5). p.252-261
Abstract
Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose - positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers NCAM, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array... (More)
Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose - positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers NCAM, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p, and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma. © 2014 Wiley Periodicals, Inc. (Less)
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International Journal of Cancer
volume
136
issue
5
pages
252 - 261
publisher
John Wiley & Sons
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  • pmid:25220031
  • wos:000346350500005
  • scopus:84918532694
ISSN
0020-7136
DOI
10.1002/ijc.29217
project
CREATE Health
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English
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yes
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8c6d4bdd-72d2-4937-b6e5-f667591b1116 (old id 4691546)
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http://www.ncbi.nlm.nih.gov/pubmed/25220031?dopt=Abstract
date added to LUP
2014-10-07 17:24:39
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2017-11-19 03:17:31
@article{8c6d4bdd-72d2-4937-b6e5-f667591b1116,
  abstract     = {Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose - positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers NCAM, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p, and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma. © 2014 Wiley Periodicals, Inc.},
  author       = {Braekeveldt, Noémie and Wigerup, Caroline and Gisselsson Nord, David and Mohlin, Sofie and Merselius, My and Beckman, Siv and Jonson, Tord and Börjesson, Anna and Backman, Torbjörn and Tadeo, Irene and Berbegall, Ana P and Øra, Ingrid and Navarro, Samuel and Noguera, Rosa and Påhlman, Sven and Bexell, Daniel},
  issn         = {0020-7136},
  language     = {eng},
  number       = {5},
  pages        = {252--261},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Neuroblastoma Patient-Derived Orthotopic Xenografts Retain Metastatic Patterns and Geno- and Phenotypes of Patient Tumours.},
  url          = {http://dx.doi.org/10.1002/ijc.29217},
  volume       = {136},
  year         = {2015},
}