Multi-omic integration of DNA methylation and gene expression data reveals molecular vulnerabilities in glioblastoma

Glioblastoma (GBM) is one of the most aggressive types of cancer and exhibits profound genetic and epigenetic heterogeneity, making the development of an effective treatment a major challenge. The recent incorporation of molecular features into the diagnosis of patients with GBM has led to an improv...

Full description

Saved in:
Bibliographic Details
Published in:Molecular oncology 2023-09, Vol.17 (9), p.1726-1743
Main Authors: Santamarina-Ojeda, Pablo, Tejedor, Juan Ramón, Pérez, Raúl F, López, Virginia, Roberti, Annalisa, Mangas, Cristina, Fernández, Agustín F, Fraga, Mario F
Format: Article
Language:English
Subjects:
Brain Cancer
Brain research
Cancer Therapies
Cbfa-1 protein
Cell culture
DNA methylation
Epigenetics
Gene expression
Genomes
Genotype & phenotype
Glioblastoma
High Throughput Techniques
Medical prognosis
Medical research
mesenchymal
Methylation
multi‐omics
Nervous system
Patients
patient‐derived GBM stem cells
Personalized Medicine
Runx1 protein
Smad3 protein
Stem cells
Temozolomide
Transcription factors
Tumors
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Glioblastoma (GBM) is one of the most aggressive types of cancer and exhibits profound genetic and epigenetic heterogeneity, making the development of an effective treatment a major challenge. The recent incorporation of molecular features into the diagnosis of patients with GBM has led to an improved categorization into various tumour subtypes with different prognoses and disease management. In this work, we have exploited the benefits of genome-wide multi-omic approaches to identify potential molecular vulnerabilities existing in patients with GBM. Integration of gene expression and DNA methylation data from both bulk GBM and patient-derived GBM stem cell lines has revealed the presence of major sources of GBM variability, pinpointing subtype-specific tumour vulnerabilities amenable to pharmacological interventions. In this sense, inhibition of the AP-1, SMAD3 and RUNX1/RUNX2 pathways, in combination or not with the chemotherapeutic agent temozolomide, led to the subtype-specific impairment of tumour growth, particularly in the context of the aggressive, mesenchymal-like subtype. These results emphasize the involvement of these molecular pathways in the development of GBM and have potential implications for the development of personalized therapeutic approaches.
ISSN:1574-7891
1878-0261
DOI:10.1002/1878-0261.13479