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dc.contributor.authorBoysen, G
dc.contributor.authorRodrigues, DN
dc.contributor.authorRescigno, P
dc.contributor.authorSeed, G
dc.contributor.authorDolling, D
dc.contributor.authorRiisnaes, R
dc.contributor.authorCrespo, M
dc.contributor.authorZafeiriou, Z
dc.contributor.authorSumanasuriya, S
dc.contributor.authorBianchini, D
dc.contributor.authorHunt, J
dc.contributor.authorMoloney, D
dc.contributor.authorPerez-Lopez, R
dc.contributor.authorTunariu, N
dc.contributor.authorMiranda, S
dc.contributor.authorFigueiredo, I
dc.contributor.authorFerreira, A
dc.contributor.authorChristova, R
dc.contributor.authorGil, V
dc.contributor.authorAziz, S
dc.contributor.authorBertan, C
dc.contributor.authorde Oliveira, FM
dc.contributor.authorAtkin, M
dc.contributor.authorClarke, M
dc.contributor.authorGoodall, J
dc.contributor.authorSharp, A
dc.contributor.authorMacDonald, T
dc.contributor.authorRubin, MA
dc.contributor.authorYuan, W
dc.contributor.authorBarbieri, CE
dc.contributor.authorCarreira, S
dc.contributor.authorMateo, J
dc.contributor.authorde Bono, JS
dc.date.accessioned2018-10-10T09:18:33Z
dc.date.issued2018-11
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2018, 24 (22), pp. 5585 - 5593
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2892
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-18-0937
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 .
dc.formatPrint-Electronic
dc.format.extent5585 - 5593
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectDisease Progression
dc.subjectAndrostenes
dc.subjectDNA Helicases
dc.subjectDNA-Binding Proteins
dc.subjectNuclear Proteins
dc.subjectRepressor Proteins
dc.subjectRNA, Small Interfering
dc.subjectNeoplasm Staging
dc.subjectGene Expression
dc.subjectGene Deletion
dc.subjectDrug Resistance, Neoplasm
dc.subjectMutation
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectNeoplasm Grading
dc.subjectSynthetic Lethal Mutations
dc.titleSPOP-Mutated/CHD1-Deleted Lethal Prostate Cancer and Abiraterone Sensitivity.
dc.typeJournal Article
dcterms.dateAccepted2018-07-25
rioxxterms.versionofrecord10.1158/1078-0432.ccr-18-0937
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue22
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/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.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/18/19 Starting Cohort
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.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/18/19 Starting Cohort
pubs.publication-statusPublished
pubs.volume24
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkersen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
icr.researchteamTranslational Therapeuticsen_US
dc.contributor.icrauthorSumanasuriya, Seminien
dc.contributor.icrauthorSeed, Georgeen
dc.contributor.icrauthorRescigno, Pasqualeen
dc.contributor.icrauthorSharp, Adamen
dc.contributor.icrauthorCarreira, Suzanneen
dc.contributor.icrauthorTunariu, Ninaen
dc.contributor.icrauthorDe Bono, Johannen
dc.contributor.icrauthorMiranda, Susanaen
dc.contributor.icrauthorCrespo, Mateusen


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