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dc.contributor.authorBrunton, H
dc.contributor.authorCaligiuri, G
dc.contributor.authorCunningham, R
dc.contributor.authorUpstill-Goddard, R
dc.contributor.authorBailey, U-M
dc.contributor.authorGarner, IM
dc.contributor.authorNourse, C
dc.contributor.authorDreyer, S
dc.contributor.authorJones, M
dc.contributor.authorMoran-Jones, K
dc.contributor.authorWright, DW
dc.contributor.authorPaulus-Hock, V
dc.contributor.authorNixon, C
dc.contributor.authorThomson, G
dc.contributor.authorJamieson, NB
dc.contributor.authorMcGregor, GA
dc.contributor.authorEvers, L
dc.contributor.authorMcKay, CJ
dc.contributor.authorGulati, A
dc.contributor.authorBrough, R
dc.contributor.authorBajrami, I
dc.contributor.authorPettitt, SJ
dc.contributor.authorDziubinski, ML
dc.contributor.authorBarry, ST
dc.contributor.authorGrützmann, R
dc.contributor.authorBrown, R
dc.contributor.authorCurry, E
dc.contributor.authorGlasgow Precision Oncology Laboratory
dc.contributor.authorAustralian Pancreatic Cancer Genome Initiative
dc.contributor.authorPajic, M
dc.contributor.authorMusgrove, EA
dc.contributor.authorPetersen, GM
dc.contributor.authorShanks, E
dc.contributor.authorAshworth, A
dc.contributor.authorCrawford, HC
dc.contributor.authorSimeone, DM
dc.contributor.authorFroeling, FEM
dc.contributor.authorLord, CJ
dc.contributor.authorMukhopadhyay, D
dc.contributor.authorPilarsky, C
dc.contributor.authorGrimmond, SE
dc.contributor.authorMorton, JP
dc.contributor.authorSansom, OJ
dc.contributor.authorChang, DK
dc.contributor.authorBailey, PJ
dc.contributor.authorBiankin, AV
dc.date.accessioned2020-07-08T11:01:28Z
dc.date.issued2020-05
dc.identifier.citationCell reports, 2020, 31 (6), pp. 107625 - ?
dc.identifier.issn2211-1247
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3827
dc.identifier.eissn2211-1247
dc.identifier.doi10.1016/j.celrep.2020.107625
dc.description.abstractPancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility to predict responsiveness and tolerance to GSK3β inhibitors. Our findings demonstrate that distinct patterns of chromatin accessibility can be used to identify patient subgroups that are indistinguishable by gene expression profiles, highlighting the utility of chromatin-based biomarkers for patient selection in the treatment of PDAC.
dc.formatPrint
dc.format.extent107625 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectGlasgow Precision Oncology Laboratory
dc.subjectAustralian Pancreatic Cancer Genome Initiative
dc.titleHNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer.
dc.typeJournal Article
dcterms.dateAccepted2020-04-17
rioxxterms.versionofrecord10.1016/j.celrep.2020.107625
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-05
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell reports
pubs.issue6
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Medicine (Brown Epigenetic Therapy)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Medicine (Brown Epigenetic Therapy)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.publication-statusPublished
pubs.volume31
pubs.embargo.termsNot known
icr.researchteamMedicine (Brown Epigenetic Therapy)en_US
icr.researchteamGene Functionen_US
dc.contributor.icrauthorLord, Christopheren
dc.contributor.icrauthorBrown, Roberten


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