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Patient-Derived Xen...
Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma
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Braekeveldt, N. (author)
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von Stedingk, K. (author)
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- Fransson, Susanne, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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- Martinez-Monleon, Angela (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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Lindgren, D. (author)
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Axelson, H. (author)
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Levander, F. (author)
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Willforss, J. (author)
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Hansson, K. (author)
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Ora, I. (author)
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Backman, T. (author)
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Borjesson, A. (author)
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Beckman, S. (author)
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Esfandyari, J. (author)
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Berbegall, A. P. (author)
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Noguera, R. (author)
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Karlsson, J. (author)
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Koster, J. (author)
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- Martinsson, Tommy, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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Gisselsson, D. (author)
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Pahlman, S. (author)
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Bexell, D. (author)
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(creator_code:org_t)
- 2018
- 2018
- English.
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In: Cancer Research. - 0008-5472. ; 78:20, s. 5958-5969
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Patient-derived xenografts (PDX) and the Avatar, a single PDX mirroring an individual patient, are emerging tools in preclinical cancer research. However, the consequences of intratumor heterogeneity for PDX modeling of biomarkers, target identification, and treatment decisions remain under-explored. In this study, we undertook serial passaging and comprehensive molecular analysis of neuroblastoma orthotopic PDXs, which revealed strong intrinsic genetic, transcriptional, and phenotypic stability for more than 2 years. The PDXs showed preserved neuroblastoma-associated gene signatures that correlated with poor clinical outcome in a large cohort of patients with neuroblastoma. Furthermore, we captured spatial intratumor heterogeneity using ten PDXs from a single high-risk patient tumor. We observed diverse growth rates, transcriptional, proteomic, and phosphoproteomic profiles. PDX-derived transcriptional profiles were associated with diverse clinical characteristics in patients with high-risk neuroblastoma. These data suggest that high-risk neuroblastoma contains elements of both temporal stability and spatial intratumor heterogeneity, the latter of which complicates clinical translation of personalized PDX-Avatar studies into preclinical cancer research. Significance: These findings underpin the complexity of PDX modeling as a means to advance translational applications against neuroblastoma. (C) 2018 AACR.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- high-risk neuroblastoma
- orthotopic xenografts
- tumor evolution
- dynamics
- cancer
- mycn
- metastasis
- expression
- mutations
- target
- Oncology
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Braekeveldt, N.
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von Stedingk, K.
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Fransson, Susann ...
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Martinez-Monleon ...
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Lindgren, D.
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Axelson, H.
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show more...
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Levander, F.
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Willforss, J.
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Hansson, K.
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Ora, I.
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Backman, T.
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Borjesson, A.
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Beckman, S.
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Esfandyari, J.
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Berbegall, A. P.
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Noguera, R.
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Karlsson, J.
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Koster, J.
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Martinsson, Tomm ...
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Gisselsson, D.
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Pahlman, S.
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Bexell, D.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Cancer Research
- By the university
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University of Gothenburg