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

Autor: Santamarina-Ojeda P; Health Research Institute of Asturias (ISPA), Spain.; Foundation for Biomedical Research and Innovation in Asturias (FINBA), Spain.; University Institute of Oncology of Asturias (IUOPA), Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain., Tejedor JR; Health Research Institute of Asturias (ISPA), Spain.; Foundation for Biomedical Research and Innovation in Asturias (FINBA), Spain.; University Institute of Oncology of Asturias (IUOPA), Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.; Nanomaterials and Nanotechnology Research Centre (CINN-CSIC), Principality of Asturias, Spain., Pérez RF; Health Research Institute of Asturias (ISPA), Spain.; Foundation for Biomedical Research and Innovation in Asturias (FINBA), Spain.; University Institute of Oncology of Asturias (IUOPA), Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.; Nanomaterials and Nanotechnology Research Centre (CINN-CSIC), Principality of Asturias, Spain., López V; Health Research Institute of Asturias (ISPA), Spain.; Foundation for Biomedical Research and Innovation in Asturias (FINBA), Spain.; University Institute of Oncology of Asturias (IUOPA), Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain., Roberti A; Health Research Institute of Asturias (ISPA), Spain.; Foundation for Biomedical Research and Innovation in Asturias (FINBA), Spain.; University Institute of Oncology of Asturias (IUOPA), Spain.; Nanomaterials and Nanotechnology Research Centre (CINN-CSIC), Principality of Asturias, Spain., Mangas C; Health Research Institute of Asturias (ISPA), Spain.; Foundation for Biomedical Research and Innovation in Asturias (FINBA), Spain.; University Institute of Oncology of Asturias (IUOPA), Spain., Fernández AF; Health Research Institute of Asturias (ISPA), Spain.; Foundation for Biomedical Research and Innovation in Asturias (FINBA), Spain.; University Institute of Oncology of Asturias (IUOPA), Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.; Nanomaterials and Nanotechnology Research Centre (CINN-CSIC), Principality of Asturias, Spain., Fraga MF; Health Research Institute of Asturias (ISPA), Spain.; Foundation for Biomedical Research and Innovation in Asturias (FINBA), Spain.; University Institute of Oncology of Asturias (IUOPA), Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain.; Nanomaterials and Nanotechnology Research Centre (CINN-CSIC), Principality of Asturias, Spain.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2023 Sep; Vol. 17 (9), pp. 1726-1743. Date of Electronic Publication: 2023 Jul 20.
DOI: 10.1002/1878-0261.13479
Abstrakt: 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.
(© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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