Proteomics

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Proteomic analysis of chemical and genetic EZH2 inhibition in diffuse intrinsic pontine glioma cell lines

ABSTRACT: Diffuse Intrinsic Pontine Glioma (DIPG) is a rare and highly aggressive pediatric tumor. The average survival time after diagnosis is less than one year. Currently, there are no effective treatments. Characteristic of DIPG is a mutation in histone H3 which leads to a substitution of Lysine 27 to Methionine (H3K27M) which deregulates Polycomb Repressive Complex 2 (PRC2), including enzymatic activity of EZH2. Previous studies have shown that inhibition of EZH2 by chemical agents decreases DIPG cell proliferation and inhibits tumor growth in vivo. My thesis project aims to confirm that EZH2 could be a therapeutic target using chemical EZH2 inhibitors, small interfering RNAs and a CRISPR/Cas9 approach in a series of DIPG tumor cell lines and to determine underlying molecular mechanisms of action.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Brain Stem Glioma

SUBMITTER: Dupuy Jean-William  

LAB HEAD: Martin Hagedorn

PROVIDER: PXD017525 | Pride | 2022-04-01

REPOSITORIES: Pride

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Publications

An EZH2 blocker sensitizes histone mutated diffuse midline glioma to cholesterol metabolism inhibitors through an off-target effect.

Rahal Farah F   Capdevielle Caroline C   Rousseau Benoit B   Izotte Julien J   Dupuy Jean-William JW   Cappellen David D   Chotard Guillaume G   Ménard Mélissa M   Charpentier Justine J   Jecko Vincent V   Caumont Charline C   Gimbert Edouard E   Grosset Christophe F CF   Hagedorn Martin M  

Neuro-oncology advances 20220101 1

<h4>Background</h4>Diffuse Midline Glioma, H3K27M-mutant (DMG) is a rare, highly aggressive pediatric tumor affecting the brainstem, and is one of the deadliest cancers. Currently available treatment options such as chemotherapy and radiotherapy do only modestly prolong survival. In this pathology, H3K27 mutations deregulate Polycomb Repressive Complex 2 (PRC2), including enzymatic activity of EZH2, which is therefore under investigation as a therapeutic target.<h4>Methods</h4>We used a chemical  ...[more]

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