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DIPG-56. PEDIATRIC GLIOMAS EXHIBIT A UNIQUE LIPID METABOLIC PHENOTYPE DISTINCT FROM ADULT GBMS

Pediatric and adult IDH-wildtype gliomas (GBM) differ in both their clinical and molecular characteristics. However, whether distinct metabolic vulnerabilities exist between these two types of malignant brain tumors is unknown. Here, we performed integrated molecular and lipidomic profiling of both...

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Autores principales: Salinas, Jennifer, Minami, Jenna, Bayley, Nicholas, Tse, Christopher, Zhu, Henan, Tum, Hong, Cloughesy, Timothy, Liau, Linda, Graber, Thomas, Nathanson, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260162/
http://dx.doi.org/10.1093/neuonc/noad073.103
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author Salinas, Jennifer
Minami, Jenna
Bayley, Nicholas
Tse, Christopher
Zhu, Henan
Tum, Hong
Cloughesy, Timothy
Liau, Linda
Graber, Thomas
Nathanson, David
author_facet Salinas, Jennifer
Minami, Jenna
Bayley, Nicholas
Tse, Christopher
Zhu, Henan
Tum, Hong
Cloughesy, Timothy
Liau, Linda
Graber, Thomas
Nathanson, David
author_sort Salinas, Jennifer
collection PubMed
description Pediatric and adult IDH-wildtype gliomas (GBM) differ in both their clinical and molecular characteristics. However, whether distinct metabolic vulnerabilities exist between these two types of malignant brain tumors is unknown. Here, we performed integrated molecular and lipidomic profiling of both adult IDHwt and pediatric gliomas to identify distinguishable lipid phenotypes and consequent vulnerabilities. This analysis revealed IDHwt gliomas have heightened de novo lipid biosynthetic programs with an elevated abundance of triacylglycerides (TAGs). By contrast, pediatric gliomas exhibited lower lipid biosynthetic capacity and contained a higher enrichment for phospholipids. As a consequence of this unique metabolic program, pediatric gliomas relied of uptake of environmental complex fatty acids derived from normal resident brain cells for growth. Accordingly, therapeutic abrogation of lipid scavenging pathways selectively inhibited proliferation of pediatric gliomas compared to adult IDHwt counterparts. Together, these studies identify distinct metabolic programs among adult and pediatric gliomas, revealing new therapeutically actionable targets to slow pediatric glioma growth.
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spelling pubmed-102601622023-06-13 DIPG-56. PEDIATRIC GLIOMAS EXHIBIT A UNIQUE LIPID METABOLIC PHENOTYPE DISTINCT FROM ADULT GBMS Salinas, Jennifer Minami, Jenna Bayley, Nicholas Tse, Christopher Zhu, Henan Tum, Hong Cloughesy, Timothy Liau, Linda Graber, Thomas Nathanson, David Neuro Oncol Final Category: Diffuse Intrinsic Pontine Glioma/Diffuse Midline Gliomas - DPIG Pediatric and adult IDH-wildtype gliomas (GBM) differ in both their clinical and molecular characteristics. However, whether distinct metabolic vulnerabilities exist between these two types of malignant brain tumors is unknown. Here, we performed integrated molecular and lipidomic profiling of both adult IDHwt and pediatric gliomas to identify distinguishable lipid phenotypes and consequent vulnerabilities. This analysis revealed IDHwt gliomas have heightened de novo lipid biosynthetic programs with an elevated abundance of triacylglycerides (TAGs). By contrast, pediatric gliomas exhibited lower lipid biosynthetic capacity and contained a higher enrichment for phospholipids. As a consequence of this unique metabolic program, pediatric gliomas relied of uptake of environmental complex fatty acids derived from normal resident brain cells for growth. Accordingly, therapeutic abrogation of lipid scavenging pathways selectively inhibited proliferation of pediatric gliomas compared to adult IDHwt counterparts. Together, these studies identify distinct metabolic programs among adult and pediatric gliomas, revealing new therapeutically actionable targets to slow pediatric glioma growth. Oxford University Press 2023-06-12 /pmc/articles/PMC10260162/ http://dx.doi.org/10.1093/neuonc/noad073.103 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Final Category: Diffuse Intrinsic Pontine Glioma/Diffuse Midline Gliomas - DPIG
Salinas, Jennifer
Minami, Jenna
Bayley, Nicholas
Tse, Christopher
Zhu, Henan
Tum, Hong
Cloughesy, Timothy
Liau, Linda
Graber, Thomas
Nathanson, David
DIPG-56. PEDIATRIC GLIOMAS EXHIBIT A UNIQUE LIPID METABOLIC PHENOTYPE DISTINCT FROM ADULT GBMS
title DIPG-56. PEDIATRIC GLIOMAS EXHIBIT A UNIQUE LIPID METABOLIC PHENOTYPE DISTINCT FROM ADULT GBMS
title_full DIPG-56. PEDIATRIC GLIOMAS EXHIBIT A UNIQUE LIPID METABOLIC PHENOTYPE DISTINCT FROM ADULT GBMS
title_fullStr DIPG-56. PEDIATRIC GLIOMAS EXHIBIT A UNIQUE LIPID METABOLIC PHENOTYPE DISTINCT FROM ADULT GBMS
title_full_unstemmed DIPG-56. PEDIATRIC GLIOMAS EXHIBIT A UNIQUE LIPID METABOLIC PHENOTYPE DISTINCT FROM ADULT GBMS
title_short DIPG-56. PEDIATRIC GLIOMAS EXHIBIT A UNIQUE LIPID METABOLIC PHENOTYPE DISTINCT FROM ADULT GBMS
title_sort dipg-56. pediatric gliomas exhibit a unique lipid metabolic phenotype distinct from adult gbms
topic Final Category: Diffuse Intrinsic Pontine Glioma/Diffuse Midline Gliomas - DPIG
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260162/
http://dx.doi.org/10.1093/neuonc/noad073.103
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