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Multi‐omic integration of DNA methylation and gene expression data reveals molecular vulnerabilities in glioblastoma
by
Cristina Mangas
, Raúl F. Pérez
, Annalisa Roberti
, Juan Ramón Tejedor
, Mario F. Fraga
, Agustín F. Fernández
, Pablo Santamarina‐Ojeda
, Virginia López
in
Brain Cancer
/ Brain Neoplasms
/ Brain research
/ Cancer Therapies
/ Cbfa-1 protein
/ Cell culture
/ DNA methylation
/ Epigenetics
/ Gene Expression
/ Genomes
/ Genotype & phenotype
/ Glioblastoma
/ High Throughput Techniques
/ Humans
/ Medical prognosis
/ Medical research
/ Mesenchymal
/ Methylation
/ Multi-omics
/ Multiomics
/ Neoplasms. Tumors. Oncology. Including cancer and carcinogens
/ Nervous system
/ Non-pharmacological intervention
/ Patient-derived GBM stem cells
/ Patients
/ Personalized Medicine
/ RC254-282
/ Runx1 protein
/ Smad3 protein
/ Stem cells
/ Temozolomide
/ Transcription factors
/ Tumors
2023
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Multi‐omic integration of DNA methylation and gene expression data reveals molecular vulnerabilities in glioblastoma
by
Cristina Mangas
, Raúl F. Pérez
, Annalisa Roberti
, Juan Ramón Tejedor
, Mario F. Fraga
, Agustín F. Fernández
, Pablo Santamarina‐Ojeda
, Virginia López
in
Brain Cancer
/ Brain Neoplasms
/ Brain research
/ Cancer Therapies
/ Cbfa-1 protein
/ Cell culture
/ DNA methylation
/ Epigenetics
/ Gene Expression
/ Genomes
/ Genotype & phenotype
/ Glioblastoma
/ High Throughput Techniques
/ Humans
/ Medical prognosis
/ Medical research
/ Mesenchymal
/ Methylation
/ Multi-omics
/ Multiomics
/ Neoplasms. Tumors. Oncology. Including cancer and carcinogens
/ Nervous system
/ Non-pharmacological intervention
/ Patient-derived GBM stem cells
/ Patients
/ Personalized Medicine
/ RC254-282
/ Runx1 protein
/ Smad3 protein
/ Stem cells
/ Temozolomide
/ Transcription factors
/ Tumors
2023
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Multi‐omic integration of DNA methylation and gene expression data reveals molecular vulnerabilities in glioblastoma
by
Cristina Mangas
, Raúl F. Pérez
, Annalisa Roberti
, Juan Ramón Tejedor
, Mario F. Fraga
, Agustín F. Fernández
, Pablo Santamarina‐Ojeda
, Virginia López
in
Brain Cancer
/ Brain Neoplasms
/ Brain research
/ Cancer Therapies
/ Cbfa-1 protein
/ Cell culture
/ DNA methylation
/ Epigenetics
/ Gene Expression
/ Genomes
/ Genotype & phenotype
/ Glioblastoma
/ High Throughput Techniques
/ Humans
/ Medical prognosis
/ Medical research
/ Mesenchymal
/ Methylation
/ Multi-omics
/ Multiomics
/ Neoplasms. Tumors. Oncology. Including cancer and carcinogens
/ Nervous system
/ Non-pharmacological intervention
/ Patient-derived GBM stem cells
/ Patients
/ Personalized Medicine
/ RC254-282
/ Runx1 protein
/ Smad3 protein
/ Stem cells
/ Temozolomide
/ Transcription factors
/ Tumors
2023
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Multi‐omic integration of DNA methylation and gene expression data reveals molecular vulnerabilities in glioblastoma
Journal Article
Multi‐omic integration of DNA methylation and gene expression data reveals molecular vulnerabilities in glioblastoma
2023
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Overview
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.
Publisher
Wiley,John Wiley & Sons, Inc,John Wiley and Sons Inc
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