Identifier to cite or link to this item: https://hdl.handle.net/20.500.13003/19490
Chromatin insulation dynamics in glioblastoma: challenges and future perspectives of precision oncology
Identifiers
ISSN: 1868-7075
eISSN: 1868-7083
WOS ID: 679793000001
Scopus EID: 2-s2.0-85111494948
PMID: 34332627
Embase PUI: L2013322809
Share
Statistics
Item usage statisticsMetadata
Show Dublin Core item recordPublication date
2021-12Document type
review articleCitation
Sese B, Ensenyat-Mendez M, Iniguez S, Llinas-Arias P, Marzese DM. Chromatin insulation dynamics in glioblastoma: challenges and future perspectives of precision oncology. Clin Epigenetics. 2021 Dec;13(1):150.Abstract
Glioblastoma (GBM) is the most aggressive primary brain tumor, having a poor prognosis and a median overall survival of less than two years. Over the last decade, numerous findings regarding the distinct molecular and genetic profiles of GBM have led to the emergence of several therapeutic approaches. Unfortunately, none of them has proven to be effective against GBM progression and recurrence. Epigenetic mechanisms underlying GBM tumor biology, including histone modifications, DNA methylation, and chromatin architecture, have become an attractive target for novel drug discovery strategies. Alterations on chromatin insulator elements (IEs) might lead to aberrant chromatin remodeling via DNA loop formation, causing oncogene reactivation in several types of cancer, including GBM. Importantly, it is shown that mutations affecting the isocitrate dehydrogenase (IDH) 1 and 2 genes, one of the most frequent genetic alterations in gliomas, lead to genome-wide DNA hypermethylation and the consequent IE dysfunction. The relevance of IEs has also been observed in a small population of cancer stem cells known as glioma stem cells (GSCs), which are thought to participate in GBM tumor initiation and drug resistance. Recent studies revealed that epigenomic alterations, specifically chromatin insulation and DNA loop formation, play a crucial role in establishing and maintaining the GSC transcriptional program. This review focuses on the relevance of IEs in GBM biology and their implementation as a potential theranostic target to stratify GBM patients and develop novel therapeutic approaches. We will also discuss the state-of-the-art emerging technologies using big data analysis and how they will settle the bases on future diagnosis and treatment strategies in GBM patients.
MeSH
Medical OncologyChromatin
Precision Medicine
DNA Methylation
Insulator Elements
Humans
Glioblastoma
DeCS
GlioblastomaHumanos
Cromatina
Metilación de ADN
Medicina de Precisión
Elementos Aisladores
Oncología Médica