American Association for Cancer Research
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00085472can180527-sup-197268_2_supp_4965948_pdhwzx.png (370.98 kB)

Figure S3 from Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma

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posted on 2023-03-31, 02:10 authored by 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

Supplementary Figure S3. Related to Figure 5. Proteomic analysis of multiple samples derived from Patient #5.

Funding

Swedish Cancer Society

Swedish Childhood Cancer Foundation

Swedish Research Council

Mrs. Berta Kamprad Foundation

SSF

Strategic Cancer Research

Crafoord Foundation

Jeanssons Stiftelser

Mary Béves Stiftelse för Barncancerforskning

Ollie och Elof Ericssons stiftelser

Berth von Kantzows stiftelse

Royal Physiographic Society in Lund

Åke Wibergs stiftelse

Tegger Foundation

Gyllenstiernska Krapperupsstiftelsen

Skåne University Hospital

Scientific Foundation Spanish Association

ISCIII

History

ARTICLE ABSTRACT

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.Significance: These findings underpin the complexity of PDX modeling as a means to advance translational applications against neuroblastoma. Cancer Res; 78(20); 5958–69. ©2018 AACR.

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