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dc.contributor.authorBoysen, Gen_US
dc.contributor.authorRodrigues, DNen_US
dc.contributor.authorRescigno, Pen_US
dc.contributor.authorSeed, Gen_US
dc.contributor.authorDolling, Den_US
dc.contributor.authorRiisnaes, Ren_US
dc.contributor.authorCrespo, Men_US
dc.contributor.authorZafeiriou, Zen_US
dc.contributor.authorSumanasuriya, Sen_US
dc.contributor.authorBianchini, Den_US
dc.contributor.authorHunt, Jen_US
dc.contributor.authorMoloney, Den_US
dc.contributor.authorPerez-Lopez, Ren_US
dc.contributor.authorTunariu, Nen_US
dc.contributor.authorMiranda, Sen_US
dc.contributor.authorFigueiredo, Ien_US
dc.contributor.authorFerreira, Aen_US
dc.contributor.authorChristova, Ren_US
dc.contributor.authorGil, Ven_US
dc.contributor.authorAziz, Sen_US
dc.contributor.authorBertan, Cen_US
dc.contributor.authorde Oliveira, FMen_US
dc.contributor.authorAtkin, Men_US
dc.contributor.authorClarke, Men_US
dc.contributor.authorGoodall, Jen_US
dc.contributor.authorSharp, Aen_US
dc.contributor.authorMacDonald, Ten_US
dc.contributor.authorRubin, MAen_US
dc.contributor.authorYuan, Wen_US
dc.contributor.authorBarbieri, CEen_US
dc.contributor.authorCarreira, Sen_US
dc.contributor.authorMateo, Jen_US
dc.contributor.authorde Bono, JSen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2018-10-10T09:18:33Z
dc.date.issued2018-11-15en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30068710en_US
dc.identifier1078-0432.CCR-18-0937en_US
dc.identifier.citationClin Cancer Res, 2018, 24 (22), pp. 5585 - 5593en_US
dc.identifier.issn1078-0432en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2892
dc.identifier.doi10.1158/1078-0432.CCR-18-0937en_US
dc.description.abstractPurpose:CHD1 deletions and SPOP mutations frequently cooccur in prostate cancer with lower frequencies reported in castration-resistant prostate cancer (CRPC). We monitored CHD1 expression during disease progression and assessed the molecular and clinical characteristics of CHD1-deleted/SPOP-mutated metastatic CRPC (mCRPC).Experimental Design: We identified 89 patients with mCRPC who had hormone-naive and castration-resistant tumor samples available: These were analyzed for CHD1, PTEN, and ERG expression by IHC. SPOP status was determined by targeted next-generation sequencing (NGS). We studied the correlations between these biomarkers and (i) overall survival from diagnosis; (ii) overall survival from CRPC; (iii) duration of abiraterone treatment; and (iv) response to abiraterone. Relationship with outcome was analyzed using Cox regression and log-rank analyses.Results: CHD1 protein loss was detected in 11 (15%) and 13 (17%) of hormone-sensitive prostate cancer (HSPC) and CRPC biopsies, respectively. Comparison of CHD1 expression was feasible in 56 matched, same patient HSPC and CRPC biopsies. CHD1 protein status in HSPC and CRPC correlated in 55 of 56 cases (98%). We identified 22 patients with somatic SPOP mutations, with six of these mutations not reported previously in prostate cancer. SPOP mutations and/or CHD1 loss was associated with a higher response rate to abiraterone (SPOP: OR, 14.50 P = 0.001; CHD1: OR, 7.30, P = 0.08) and a longer time on abiraterone (SPOP: HR, 0.37, P = 0.002, CHD1: HR, 0.50, P = 0.06).Conclusions:SPOP-mutated mCRPCs are strongly enriched for CHD1 loss. These tumors appear highly sensitive to abiraterone treatment. Clin Cancer Res; 24(22); 5585-93. ©2018 AACR.en_US
dc.format.extent5585 - 5593en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleSPOP-Mutated/CHD1-Deleted Lethal Prostate Cancer and Abiraterone Sensitivity.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-07-25en_US
rioxxterms.versionofrecord10.1158/1078-0432.CCR-18-0937en_US
rioxxterms.licenseref.startdate2018-11-15en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfClin Cancer Resen_US
pubs.issue22en_US
pubs.notesNot knownen_US
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.publication-statusPublisheden_US
pubs.volume24en_US
pubs.embargo.termsNot knownen_US
icr.researchteamCancer Biomarkersen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorDe Bono, Johannen_US
dc.contributor.icrauthorCarreira, Suzanneen_US
dc.contributor.icrauthorTunariu, Ninaen_US


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