H3.3K27M Mutation Controls Cell Growth and Resistance to Therapies in Pediatric Glioma Cell Lines

Rakotomalala, Andria; Bailleul, Quentin; Savary, Clara; Arcicasa, Mélanie; Hamadou, Maud; Huchedé, Paul; Hochart, Audrey; Restouin, Audrey; Castellano, Remy; Collette, Yves; Dieny, Emma; Vincent, Audrey; Angrand, Pierre-Olivier; Le Bourhis, Xuefen; Leblond, Pierre; Furlan, Alessandro; Castets, Marie; Pasquier, Eddy; Meignan, Samuel

Document type :

Compte-rendu et recension critique d'ouvrage

DOI :

10.3390/cancers13215551

Permalink :

http://hdl.handle.net/20.500.12210/108063

Title :

H3.3K27M Mutation Controls Cell Growth and Resistance to Therapies in Pediatric Glioma Cell Lines

Author(s) :

Rakotomalala, Andria [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Bailleul, Quentin [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Savary, Clara [Auteur]
Centre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
Arcicasa, Mélanie [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Hamadou, Maud [Auteur]
Centre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
Huchedé, Paul [Auteur]
Centre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
Hochart, Audrey [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Restouin, Audrey [Auteur]
Centre de Recherche en Cancérologie de Marseille [CRCM]
Castellano, Remy [Auteur]
Centre de Recherche en Cancérologie de Marseille [CRCM]
Collette, Yves [Auteur]
Centre de Recherche en Cancérologie de Marseille [CRCM]
Dieny, Emma [Auteur]
Centre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
Vincent, Audrey [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Angrand, Pierre-Olivier [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Le Bourhis, Xuefen [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Leblond, Pierre [Auteur]
Centre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
Furlan, Alessandro [Auteur]

Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Castets, Marie [Auteur]
Centre de Recherche en Cancérologie de Lyon [UNICANCER/CRCL]
Pasquier, Eddy [Auteur]
Centre de Recherche en Cancérologie de Marseille [CRCM]
Meignan, Samuel [Auteur correspondant]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]

Journal title :

Cancers

Pages :

5551

Publisher :

MDPI

Publication date :

2021

ISSN :

2072-6694

English keyword(s) :

H3.3K27M
glioma
child
resistance to therapies
radiotherapy

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Pédiatrie
Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC]/Neurobiologie
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]

English abstract : [en]

High-grade gliomas represent the most lethal class of pediatric tumors, and their resistance to both radio- and chemotherapy is associated with a poor prognosis. Recurrent mutations affecting histone genes drive the ...
Show more >High-grade gliomas represent the most lethal class of pediatric tumors, and their resistance to both radio- and chemotherapy is associated with a poor prognosis. Recurrent mutations affecting histone genes drive the tumorigenesis of some pediatric high-grade gliomas, and H3K27M mutations are notably characteristic of a subtype of gliomas called DMG (Diffuse Midline Gliomas). This dominant negative mutation impairs H3K27 trimethylation, leading to profound epigenetic modifications of genes expression. Even though this mutation was described as a driver event in tumorigenesis, its role in tumor cell resistance to treatments has not been deciphered so far. To tackle this issue, we expressed the H3.3K27M mutated histone in three initially H3K27-unmutated pediatric glioma cell lines, Res259, SF188, and KNS42. First, we validated these new H3.3K27M-expressing models at the molecular level and showed that K27M expression is associated with pleiotropic effects on the transcriptomic signature, largely dependent on cell context. We observed that the mutation triggered an increase in cell growth in Res259 and SF188 cells, associated with higher clonogenic capacities. Interestingly, we evidenced that the mutation confers an increased resistance to ionizing radiations in Res259 and KNS42 cells. Moreover, we showed that H3.3K27M mutation impacts the sensitivity of Res259 cells to specific drugs among a library of 80 anticancerous compounds. Altogether, these data highlight that, beyond its tumorigenic role, H3.3K27M mutation is strongly involved in pediatric glioma cells’ resistance to therapies, likely through transcriptomic reprogrammingShow less >

Language :

Anglais

Popular science :

Non

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