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Patient-derived xen...
Patient-derived xenograft models reveal intratumor heterogeneity and temporal stability in neuroblastoma
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- Braekeveldt, Noémie (author)
- Lund University,Lunds universitet,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,Molecular Pediatric Oncology,Lund University Research Groups
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- Von Stedingk, Kristoffer (author)
- Lund University,Lunds universitet,Childhood Cancer Research Unit,Forskargrupper vid Lunds universitet,Lund University Research Groups,Academic Medical Center of University of Amsterdam (AMC),Skåne University Hospital,University of Amsterdam
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- Fransson, Susanne (author)
- University of Gothenburg
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- Martinez-Monleon, Angela (author)
- University of Gothenburg
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- Lindgren, David (author)
- Lund University,Lunds universitet,Njurcancergruppen,Forskargrupper vid Lunds universitet,Kidney cancer research group,Lund University Research Groups
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- Axelson, Håkan (author)
- Lund University,Lunds universitet,Njurcancergruppen,Forskargrupper vid Lunds universitet,Kidney cancer research group,Lund University Research Groups
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- Levander, Fredrik (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Willforss, Jakob (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Hansson, Karin (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH
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- Øra, Ingrid (author)
- Lund University,Lunds universitet,Childhood Cancer Research Unit,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital
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- Backman, Torbjörn (author)
- Lund University,Lunds universitet,Barnkirurgi,Forskargrupper vid Lunds universitet,Pediatric surgery,Lund University Research Groups,Skåne University Hospital
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- Börjesson, Anna (author)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Beckman, Siv (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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- Esfandyari, Javanshir (author)
- Lund University,Lunds universitet,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,Molecular Pediatric Oncology,Lund University Research Groups
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- Berbegall, Ana P. (author)
- Spanish Center for Biomedical Research Network in Oncology (CIBERONC),University of Valencia
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- Noguera, Rosa (author)
- Spanish Center for Biomedical Research Network in Oncology (CIBERONC),University of Valencia
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- Karlsson, Jenny (author)
- Lund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,Pathways of cancer cell evolution,Lund University Research Groups
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- Koster, Jan (author)
- Academic Medical Center of University of Amsterdam (AMC)
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- Martinsson, Tommy (author)
- University of Gothenburg
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- Gisselsson, David (author)
- Lund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,Pathways of cancer cell evolution,Lund University Research Groups,Skåne University Hospital
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- Påhlman, Sven (author)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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- Bexell, Daniel (author)
- Lund University,Lunds universitet,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,Molecular Pediatric Oncology,Lund University Research Groups,Skåne University Hospital
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(creator_code:org_t)
- 2018
- 2018
- English 12 s.
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In: Cancer Research. - 0008-5472. ; 78:20, s. 5958-5969
- Related links:
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http://dx.doi.org/10...
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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 underexplored. 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Braekeveldt, Noé ...
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Von Stedingk, Kr ...
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Fransson, Susann ...
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Martinez-Monleon ...
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Lindgren, David
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Axelson, Håkan
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Levander, Fredri ...
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Willforss, Jakob
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Hansson, Karin
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Øra, Ingrid
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Backman, Torbjör ...
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Börjesson, Anna
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Beckman, Siv
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Esfandyari, Java ...
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Berbegall, Ana P ...
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Noguera, Rosa
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Karlsson, Jenny
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Koster, Jan
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Martinsson, Tomm ...
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Gisselsson, Davi ...
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Påhlman, Sven
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Bexell, Daniel
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Cancer Research
- By the university
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Lund University