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Stem cell cultures derived from pediatric brain tumors accurately model the originating tumors.

Journal article
Authors Anna Wenger
Susanna Larsson
Anna Danielsson
Kirstine Juul Elbæk
Petronella Kettunen
Magnus Tisell
Magnus Sabel
Birgitta Lannering
Claes Nordborg
Elizabeth Schepke
Helena Carén
Published in Oncotarget
Volume 8
Pages 18626-18639
ISSN 1949-2553
Publication year 2017
Published at Institute of Clinical Sciences, Department of Oncology
Sahlgrenska Cancer Center
Institute of Biomedicine, Department of Pathology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Institute of Clinical Sciences, Department of Pediatrics
Pages 18626-18639
Language en
Links dx.doi.org/10.18632/oncotarget.1482...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Pediatrics

Abstract

Brain tumors are the leading cause of cancer-related death in children but high-grade gliomas in children and adolescents have remained a relatively under-investigated disease despite this. A better understanding of the cellular and molecular pathogenesis of the diseases is required in order to improve the outcome for these children. In vitro-cultured primary tumor cells from patients are indispensable tools for this purpose by enabling functional analyses and development of new therapies. However, relevant well-characterized in vitro cultures from pediatric gliomas cultured under serum-free conditions have been lacking. We have therefore established patient-derived in vitro cultures and performed thorough characterization of the cells using large-scale analyses of DNA methylation, copy-number alterations and investigated their stability during prolonged time in culture. We show that the cells were stable during prolonged culture in serum-free stem cell media without apparent alterations in morphology or growth rate. The cells were proliferative, positive for stem cell markers, able to respond to differentiation cues and initiated tumors in zebrafish and mice suggesting that the cells are cancer stem cells or progenitor cells. The cells accurately mirrored the tumor they were derived from in terms of methylation pattern, copy number alterations and DNA mutations. These unique primary in vitro cultures can thus be used as a relevant and robust model system for functional studies on pediatric brain tumors.

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