FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2084370773> ?p ?o ?g. }

• W2084370773 abstract "Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCGlioblastomas of children and young adults (pGBM) have a median survival of only 12-15 months and are clinically and biologically distinct from histologically similar cancers in older adults. They are defined by highly specific mutations in the gene encoding the histone H3.3 variant H3F3A, occurring either at or close to key residues marked by methylation for regulation of transcription - K27 and G34. The G34 mutation is specific to tumours of the cerebral hemispheres and is associated with a distinct age of incidence (16 yrs) and gene expression signature compared to K27 and wild-type tumours. ChIP-Seq for the activating K36 trimethylation mark (H3K36me3) mark of G34V mutant KNS42 pGBM cells identified 156 genes differentially bound and expressed compared to wild-type pGBM control. The transcriptional program induced recapitulates that of the developing forebrain, and involves numerous markers of stem cell maintenance, cell fate decisions and self-renewal. Critically, H3F3A G34 mutations cause profound upregulation of MYCN, a potent oncogene which is causative of glioblastomas when expressed in the correct developmental context. A synthetic lethality siRNA screen revealed this driving aberration to be selectively targetable in this patient population by inhibiting kinases responsible for stabilisation of the protein such as AURKA and CHK1. We thus provide the mechanistic explanation for how the first histone gene mutation in human disease biology acts to deliver MYCN, a potent tumorigenic initiator, into a stem cell compartment of the developing forebrain, selectively giving rise to incurable cerebral hemispheric glioblastoma. Employing synthetic lethal approaches to these mutant tumour cells provides a rational way to develop novel and highly selective treatment strategies.Citation Format: Lynn Bjerke, Alan Mackay, Meera Nandhabalan, Anna Burford, Alexa Jury, Sergey Popov, Dorine Bax, Diana Carvalho, Katy Taylor, Mara Vinci, Illirjana Bajrami, Imelda McGonnell, Chris Lord, Rui Reis, Darren Hargrave, Alan Ashworth, Paul Workman, Chris Jones. Histone H3.3 mutations drive paediatric glioblastoma through upregulation of MYCN. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2962. doi:10.1158/1538-7445.AM2013-2962Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend." @default.
• W2084370773 created "2016-06-24" @default.
• W2084370773 creator A5003965204 @default.
• W2084370773 creator A5006865176 @default.
• W2084370773 creator A5013529173 @default.
• W2084370773 creator A5016790809 @default.
• W2084370773 creator A5018676630 @default.
• W2084370773 creator A5018808600 @default.
• W2084370773 creator A5031621086 @default.
• W2084370773 creator A5035432368 @default.
• W2084370773 creator A5036350682 @default.
• W2084370773 creator A5036639927 @default.
• W2084370773 creator A5046271359 @default.
• W2084370773 creator A5058973407 @default.
• W2084370773 creator A5072470314 @default.
• W2084370773 creator A5073016473 @default.
• W2084370773 creator A5073507471 @default.
• W2084370773 creator A5076164325 @default.
• W2084370773 creator A5084263321 @default.
• W2084370773 creator A5088639706 @default.
• W2084370773 date "2013-04-15" @default.
• W2084370773 modified "2023-09-24" @default.
• W2084370773 title "Abstract 2962: Histone H3.3 mutations drive paediatric glioblastoma through upregulation of MYCN." @default.
• W2084370773 doi "https://doi.org/10.1158/1538-7445.am2013-2962" @default.
• W2084370773 hasPublicationYear "2013" @default.
• W2084370773 type Work @default.
• W2084370773 sameAs 2084370773 @default.
• W2084370773 citedByCount "0" @default.
• W2084370773 crossrefType "proceedings-article" @default.
• W2084370773 hasAuthorship W2084370773A5003965204 @default.
• W2084370773 hasAuthorship W2084370773A5006865176 @default.
• W2084370773 hasAuthorship W2084370773A5013529173 @default.
• W2084370773 hasAuthorship W2084370773A5016790809 @default.
• W2084370773 hasAuthorship W2084370773A5018676630 @default.
• W2084370773 hasAuthorship W2084370773A5018808600 @default.
• W2084370773 hasAuthorship W2084370773A5031621086 @default.
• W2084370773 hasAuthorship W2084370773A5035432368 @default.
• W2084370773 hasAuthorship W2084370773A5036350682 @default.
• W2084370773 hasAuthorship W2084370773A5036639927 @default.
• W2084370773 hasAuthorship W2084370773A5046271359 @default.
• W2084370773 hasAuthorship W2084370773A5058973407 @default.
• W2084370773 hasAuthorship W2084370773A5072470314 @default.
• W2084370773 hasAuthorship W2084370773A5073016473 @default.
• W2084370773 hasAuthorship W2084370773A5073507471 @default.
• W2084370773 hasAuthorship W2084370773A5076164325 @default.
• W2084370773 hasAuthorship W2084370773A5084263321 @default.
• W2084370773 hasAuthorship W2084370773A5088639706 @default.
• W2084370773 hasConcept C104317684 @default.
• W2084370773 hasConcept C121608353 @default.
• W2084370773 hasConcept C41091548 @default.
• W2084370773 hasConcept C502942594 @default.
• W2084370773 hasConcept C54355233 @default.
• W2084370773 hasConcept C64927066 @default.
• W2084370773 hasConcept C71924100 @default.
• W2084370773 hasConcept C86803240 @default.
• W2084370773 hasConceptScore W2084370773C104317684 @default.
• W2084370773 hasConceptScore W2084370773C121608353 @default.
• W2084370773 hasConceptScore W2084370773C41091548 @default.
• W2084370773 hasConceptScore W2084370773C502942594 @default.
• W2084370773 hasConceptScore W2084370773C54355233 @default.
• W2084370773 hasConceptScore W2084370773C64927066 @default.
• W2084370773 hasConceptScore W2084370773C71924100 @default.
• W2084370773 hasConceptScore W2084370773C86803240 @default.
• W2084370773 hasLocation W20843707731 @default.
• W2084370773 hasOpenAccess W2084370773 @default.
• W2084370773 hasPrimaryLocation W20843707731 @default.
• W2084370773 hasRelatedWork W1998675054 @default.
• W2084370773 hasRelatedWork W2070580553 @default.
• W2084370773 hasRelatedWork W2072589624 @default.
• W2084370773 hasRelatedWork W2074244064 @default.
• W2084370773 hasRelatedWork W2074262125 @default.
• W2084370773 hasRelatedWork W2075708236 @default.
• W2084370773 hasRelatedWork W2109173300 @default.
• W2084370773 hasRelatedWork W2145702674 @default.
• W2084370773 hasRelatedWork W2162794030 @default.
• W2084370773 hasRelatedWork W2395553584 @default.
• W2084370773 hasRelatedWork W2515680837 @default.
• W2084370773 hasRelatedWork W2594234949 @default.
• W2084370773 hasRelatedWork W2773306487 @default.
• W2084370773 hasRelatedWork W2901730480 @default.
• W2084370773 hasRelatedWork W2914404046 @default.
• W2084370773 hasRelatedWork W2918280605 @default.
• W2084370773 hasRelatedWork W2972514011 @default.
• W2084370773 hasRelatedWork W3041944486 @default.
• W2084370773 hasRelatedWork W3090570733 @default.
• W2084370773 hasRelatedWork W3139436654 @default.
• W2084370773 isParatext "false" @default.
• W2084370773 isRetracted "false" @default.
• W2084370773 magId "2084370773" @default.
• W2084370773 workType "article" @default.