Epigenetic mechanisms regulating neural development and pediatric brain tumor formation

Faria, Cláudia C.; Rutka, James T.; Smith, Christian A.; Kongkham, Paul

doi:10.3171/2011.5.peds1140

Cited by 13 publications

(26 citation statements)

References 156 publications

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“…DNA methylation is an increasingly important tool when it comes to tumor classification [19] and has been shown to play an important role in pediatric brain tumors [22]. Previous studies have shown that tumors, briefly cultured primary cells and cell lines have different methylation profiles and cluster separately [23, 24].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2017

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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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Section: Resultsmentioning

confidence: 99%

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

et al. 2017

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“…Epigenetics refer to studies of mitotically heritable modifications in gene expression that do not involve changes in DNA sequence, presenting a link between genotype and phenotype. In DNA replication the paternal epigenetic information is translated by enzymes known as "readers" which lead to the recruitment of other proteins termed as "writers", or "erasers" and preserve this information in the daughter strands (10). The main epigenetic mechanisms are DNA methylation, histone modifications and small noncoding RNAs (miRNAs).…”

Section: Epigenetic Mechanisms In Tumor Developmentmentioning

confidence: 99%

“…CpG nucleotides are frequently found at the 5' end of the gene promoter and/or the first exon region as big clusters, termed CpG islands (8). The CpG nucleotides inside CpG islands are usually unmethylated, but more than 80% of those traced outside of CpG islands are commonly found methylated (10). DNA methyltransferases (DNMTs) are catalyzing the reaction of methylation and can be distinguished into two subgroups: maintenance methylation and de novo methylation (10).…”

Section: Epigenetic Mechanisms In Tumor Developmentmentioning

confidence: 99%

“…The CpG nucleotides inside CpG islands are usually unmethylated, but more than 80% of those traced outside of CpG islands are commonly found methylated (10). DNA methyltransferases (DNMTs) are catalyzing the reaction of methylation and can be distinguished into two subgroups: maintenance methylation and de novo methylation (10). The maintenance methyltransferase DNMT1 is responsible for restoration of the parental DNA methylation pattern.…”

Section: Epigenetic Mechanisms In Tumor Developmentmentioning

confidence: 99%

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Chromatin remodeling defects in pediatric brain tumors

et al. 2018

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Brain tumors are regarded as the most prevalent solid neoplasms in children and the principal reason of death in this population. Even though surgical resection, radiotherapy and chemotherapy have improved outcome, a significant number of patients die in 6-12 months after diagnosis while those who survive, frequently experience side effects and relapses. Several studies suggest that many types of cancer including pediatric brain tumors are characterized by alterations in epigenetic profiles with deregulated chromatin remodeling and posttranslational covalent histone modifications playing a prominent role. Moreover, interplay of genetic and epigenetic changes has been associated to tumor growth and invasion as well as to modulation of patient's response to current treatment. Therefore, detection of tumor-specific histone changes and elucidation of the underlying gene defects will allow successful tailoring of personalized treatment. The goal of this review is to provide an update of genetic and epigenetic alterations that characterize pediatric brain tumors focusing on histone modifications, aiming at directing future molecular and epigenetic therapeutic targeting.

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“…The H3K27me3 modification regulates the expression of genes associated with lineage commitment, cellular differentiation, and anterior-posterior patterning (Faria et al 2011;Grossniklaus and Paro 2014). Thus, H3K27 has a role in normal brain development.…”

mentioning

confidence: 99%