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dc.contributor.authorMerson, S
dc.contributor.authorYang, ZH
dc.contributor.authorBrewer, D
dc.contributor.authorOlmos, D
dc.contributor.authorEichholz, A
dc.contributor.authorMcCarthy, F
dc.contributor.authorFisher, G
dc.contributor.authorKovacs, G
dc.contributor.authorBerney, DM
dc.contributor.authorFoster, CS
dc.contributor.authorMoller, H
dc.contributor.authorScardino, P
dc.contributor.authorCuzick, J
dc.contributor.authorCooper, CS
dc.contributor.authorClark, JP
dc.contributor.authorGrp, TP
dc.date.accessioned2018-08-03T11:52:01Z
dc.date.issued2014-03-18
dc.identifier6
dc.identifier.citationBRITISH JOURNAL OF CANCER, 2014, 110 pp. 1655 - 1662
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2258
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/bjc.2014.13
dc.description.abstractBackground: Androgen receptor (AR)-gene amplification, found in 20-30% of castration-resistant prostate cancer (CRPCa) is proposed to develop as a consequence of hormone-deprivation therapy and be a prime cause of treatment failure. Here we investigate AR-gene amplification in cancers before hormone deprivation therapy. Methods: A tissue microarray (TMA) series of 596 hormone-naive prostate cancers (HNPCas) was screened for chromosome X and AR-gene locus-specific copy number alterations using four-colour fluorescence in situ hybridisation. Results: Both high level gain in chromosome X (>= 4 fold; n =4, 0.7%) and locus-specific amplification of the AR-gene (n =6, 1%) were detected at low frequencies in HNPCa TMAs. Fluorescence in situ hybridisation mapping whole sections taken from the original HNPCa specimen blocks demonstrated that AR-gene amplifications exist in small foci of cells (<= 600 nm, <= 1% of tumour volume). Patients with AR gene-locus-specific copy number gains had poorer prostate cancer-specific survival. Conclusion: Small clonal foci of cancer containing high level gain of the androgen receptor (AR)-gene develop before hormone deprivation therapy. Their small size makes detection by TMA inefficient and suggests a higher prevalence than that reported herein. It is hypothesised that a large proportion of AR-amplified CRPCa could pre-date hormone deprivation therapy and that these patients would potentially benefit from early total androgen ablation.
dc.format.extent1655 - 1662
dc.languageeng
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleFocal amplification of the androgen receptor gene in hormone-naive human prostate cancer
dc.typeJournal Article
rioxxterms.versionofrecord10.1038/bjc.2014.13
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2014-03-18
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBRITISH JOURNAL OF CANCER
pubs.notesaffiliation: Clark, JP (Reprint Author), Univ E Anglia, Dept Canc Genet, Norwich NR4 7TJ, Norfolk, England. Merson, S.; Brewer, D.; Eichholz, A.; McCarthy, F., Male Urol Canc Res Ctr, Inst Canc Res, Sutton, Surrey, England. Yang, Z. H.; Fisher, G.; Moller, H.; Cuzick, J., Univ London, St Bartholomews Med Sch, Wolfson Inst Prevent Med, Ctr Canc Prevent, London, England. Brewer, D.; Cooper, C. S.; Clark, J. P., Univ E Anglia, Dept Canc Genet, Norwich NR4 7TJ, Norfolk, England. Olmos, D., Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain. Kovacs, G., Heidelberg Univ, Fac Med, Lab Mol Oncol, Heidelberg, Germany. Berney, D. M., Barts Canc Inst, Dept Mol Oncol, London, England. Foster, C. S., Univ Liverpool, Mol Pathol Lab, Liverpool L69 3BX, Merseyside, England. Foster, C. S., HCA Labs, London, England. Moller, H., Kings Coll London, London WC2R 2LS, England. Scardino, P., Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10021 USA. keywords: androgen receptor gene amplification; FISH; hormone naive; prostate cancer prognosis keywords-plus: DEPRIVATION; PROGRESSION; CELLS; ERG research-areas: Oncology web-of-science-categories: Oncology author-email: [email protected] researcherid-numbers: Brewer, Daniel/D-6201-2018 orcid-numbers: Brewer, Daniel/0000-0003-4753-9794 Moller, Henrik/0000-0001-8200-5929 Berney, Daniel/0000-0001-5474-8696 funding-acknowledgement: International Association of Cancer research; Bob Champion Cancer Trust; Grand Charity of Freemasons; Big C Cancer Charity; Orchid and Prostate Cancer UK funding-text: This work was funded by the International Association of Cancer research, the Bob Champion Cancer Trust, the Grand Charity of Freemasons, the Big C Cancer Charity, Orchid and Prostate Cancer UK. number-of-cited-references: 30 times-cited: 13 usage-count-last-180-days: 0 usage-count-since-2013: 6 journal-iso: Br. J. Cancer doc-delivery-number: AD4DB unique-id: ISI:000333195800030 oa: gold_or_bronze da: 2018-08-03
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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.volume110en_US
pubs.embargo.termsNot known
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorMerson, Susanen


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