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Håkan Axelson

Håkan Axelson

Research team manager

Håkan Axelson

Patient-derived xenograft models reveal intratumor heterogeneity and temporal stability in neuroblastoma

Author

  • Noémie Braekeveldt
  • Kristoffer Von Stedingk
  • Susanne Fransson
  • Angela Martinez-Monleon
  • David Lindgren
  • Håkan Axelson
  • Fredrik Levander
  • Jakob Willforss
  • Karin Hansson
  • Ingrid Øra
  • Torbjörn Backman
  • Anna Börjesson
  • Siv Beckman
  • Javanshir Esfandyari
  • Ana P. Berbegall
  • Rosa Noguera
  • Jenny Karlsson
  • Jan Koster
  • Tommy Martinsson
  • David Gisselsson
  • Sven Påhlman
  • Daniel Bexell
Show all

Summary, in English

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.

Department/s

  • Molecular Pediatric Oncology
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • Childhood Cancer Research Unit
  • Kidney cancer research group
  • Department of Immunotechnology
  • Pediatric surgery
  • Paediatrics (Lund)
  • Division of Translational Cancer Research
  • Pathways of cancer cell evolution

Publishing year

2018

Language

English

Pages

5958-5969

Publication/Series

Cancer Research

Volume

78

Issue

20

Document type

Journal article

Publisher

American Association for Cancer Research Inc.

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Molecular Pediatric Oncology
  • Childhood Cancer Research Unit
  • Kidney cancer research group
  • Pediatric surgery
  • Pathways of cancer cell evolution

ISBN/ISSN/Other

  • ISSN: 0008-5472