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Accumulation of DNA methylation alterations in paediatric glioma stem cells following fractionated dose irradiation

Journal article
Authors Anna Danielsson
Kristell Barreau
Teresia Kling
Magnus Tisell
Helena Carén
Published in Clinical Epigenetics
Volume 12
Issue 1
ISSN 1868-7075
Publication year 2020
Published at Institute of Clinical Sciences, Department of Oncology
Sahlgrenska Cancer Center
Department of Laboratory Medicine
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Language en
Links dx.doi.org/10.1186/s13148-020-0817-...
Keywords Epigenetics, DNA methylation, Radiation, Paediatric, Glioblastoma, Cancer stem cells, Genomic feature analysis, Repetitive DNA elements, Cancer treatment, ionizing-radiation, cancer, hypermethylation, hypomethylation, mir-b-10, Oncology, Genetics & Heredity
Subject categories Medical Genetics, Cancer and Oncology

Abstract

Background Radiation is an important therapeutic tool. However, radiotherapy has the potential to promote co-evolution of genetic and epigenetic changes that can drive tumour heterogeneity, formation of radioresistant cells and tumour relapse. There is a clinical need for a better understanding of DNA methylation alterations that may follow radiotherapy to be able to prevent the development of radiation-resistant cells. Methods We examined radiation-induced changes in DNA methylation profiles of paediatric glioma stem cells (GSCs) in vitro. Five GSC cultures were irradiated in vitro with repeated doses of 2 or 4 Gy. Radiation was given in 3 or 15 fractions. DNA methylation profiling using Illumina DNA methylation arrays was performed at 14 days post-radiation. The cellular characteristics were studied in parallel. Results Few fractions of radiation did not result in significant accumulation of DNA methylation alterations. However, extended dose fractionations changed DNA methylation profiles and induced thousands of differentially methylated positions, specifically in enhancer regions, sites involved in alternative splicing and in repetitive regions. Radiation induced dose-dependent morphological and proliferative alterations of the cells as a consequence of the radiation exposure. Conclusions DNA methylation alterations of sites with regulatory functions in proliferation and differentiation were identified, which may reflect cellular response to radiation stress through epigenetic reprogramming and differentiation cues.

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Utskriftsdatum: 2020-08-13