Your browser doesn't support javascript.
loading
Metabologenomic characterization uncovers a clinically aggressive IDH mutant glioma subtype.
Nassiri, Farshad; Ajisebutu, Andrew; Patil, Vikas; Mamatjan, Yasin; Liu, Jeff; Wang, Justin Z; Voisin, Mathew R; Nejad, Romina; Mansouri, Sheila; Karimi, Shirin; Chakravarthy, Ankur; Chen, Eric; De Carvalho, Daniel D; Aldape, Kenneth; Zadeh, Gelareh.
Affiliation
  • Nassiri F; Princess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada. farshad.nassiri@uhn.ca.
  • Ajisebutu A; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada. farshad.nassiri@uhn.ca.
  • Patil V; Princess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada.
  • Mamatjan Y; Princess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada.
  • Liu J; Princess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada.
  • Wang JZ; Princess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada.
  • Voisin MR; Princess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada.
  • Nejad R; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.
  • Mansouri S; Princess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada.
  • Karimi S; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.
  • Chakravarthy A; Princess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada.
  • Chen E; Princess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada.
  • De Carvalho DD; Princess Margaret Cancer Centre, MacFeeters Hamilton Neuro-Oncology Program, University Health Network and University of Toronto, Toronto, ON, Canada.
  • Aldape K; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Zadeh G; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Acta Neuropathol ; 147(1): 68, 2024 04 07.
Article in En | MEDLINE | ID: mdl-38583102
ABSTRACT
Mutations in the pivotal metabolic isocitrate dehydrogenase (IDH) enzymes are recognized to drive the molecular footprint of diffuse gliomas, and patients with IDH mutant gliomas have overall favorable outcomes compared to patients with IDH wild-type tumors. However, survival still varies widely among patients with IDH mutated tumors. Here, we aimed to characterize molecular signatures that explain the range of IDH mutant gliomas. By integrating matched epigenome-wide methylome, transcriptome, and global metabolome data in 154 patients with gliomas, we identified a group of IDH mutant gliomas with globally altered metabolism that resembled IDH wild-type tumors. IDH-mutant gliomas with altered metabolism have significantly shorter overall survival from their IDH mutant counterparts that is not fully accounted for by recognized molecular prognostic markers of CDKN2A/B loss and glioma CpG Island Methylator Phenotype (GCIMP) status. IDH-mutant tumors with dysregulated metabolism harbored distinct epigenetic alterations that converged to drive proliferative and stem-like transcriptional profiles, providing a window to target novel dependencies in gliomas.
Subject(s)
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Glioma / Isocitrate Dehydrogenase Limits: Humans Language: En Journal: Acta Neuropathol Year: 2024 Type: Article Affiliation country: Canada
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Glioma / Isocitrate Dehydrogenase Limits: Humans Language: En Journal: Acta Neuropathol Year: 2024 Type: Article Affiliation country: Canada