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dc.contributor.authorLi, Y
dc.contributor.authorYang, R
dc.contributor.authorHenzler, CM
dc.contributor.authorHo, Y
dc.contributor.authorPassow, C
dc.contributor.authorAuch, B
dc.contributor.authorCarreira, S
dc.contributor.authorNava Rodrigues, D
dc.contributor.authorBertan, C
dc.contributor.authorHwang, TH
dc.contributor.authorQuigley, DA
dc.contributor.authorDang, HX
dc.contributor.authorMorrissey, C
dc.contributor.authorFraser, M
dc.contributor.authorPlymate, SR
dc.contributor.authorMaher, CA
dc.contributor.authorFeng, FY
dc.contributor.authorde Bono, JS
dc.contributor.authorDehm, SM
dc.date.accessioned2020-03-04T15:32:56Z
dc.date.issued2020-04
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2020, 26 (8), pp. 1965 - 1976
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3531
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-19-3023
dc.description.abstractPurpose: Prostate cancer is the second leading cause of male cancer deaths. Castration-resistant prostate cancer (CRPC) is a lethal stage of the disease that emerges when endocrine therapies are no longer effective at suppressing activity of the androgen receptor (AR) transcription factor. The purpose of this study was to identify genomic mechanisms that contribute to the development and progression of CRPC. Experimental design: We used whole-genome and targeted DNA-sequencing approaches to identify mechanisms underlying CRPC in an aggregate cohort of 272 prostate cancer patients. We analyzed structural rearrangements at the genome-wide level and carried out a detailed structural rearrangement analysis of the AR locus. We used genome engineering to perform experimental modeling of AR gene rearrangements and long-read RNA sequencing to analyze effects on expression of AR and truncated AR variants (AR-V). Results: AR was among the most frequently rearranged genes in CRPC tumors. AR gene rearrangements promoted expression of diverse AR-V species. AR gene rearrangements occurring in the context of AR amplification correlated with AR overexpression. Cell lines with experimentally derived AR gene rearrangements displayed high expression of tumor-specific AR-Vs and were resistant to endocrine therapies, including the AR antagonist enzalutamide. Conclusions: AR gene rearrangements are an important mechanism of resistance to endocrine therapies in CRPC.
dc.formatPrint-Electronic
dc.format.extent1965 - 1976
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.titleDiverse <i>AR</i> Gene Rearrangements Mediate Resistance to Androgen Receptor Inhibitors in Metastatic Prostate Cancer.
dc.typeJournal Article
dcterms.dateAccepted2020-01-09
rioxxterms.versionofrecord10.1158/1078-0432.ccr-19-3023
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2020-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue8
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
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-statusPublished
pubs.volume26
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkersen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorCarreira, Suzanneen
dc.contributor.icrauthorDe Bono, Johannen


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