dc.contributor.author | Mateo, J | |
dc.contributor.author | Seed, G | |
dc.contributor.author | Bertan, C | |
dc.contributor.author | Rescigno, P | |
dc.contributor.author | Dolling, D | |
dc.contributor.author | Figueiredo, I | |
dc.contributor.author | Miranda, S | |
dc.contributor.author | Nava Rodrigues, D | |
dc.contributor.author | Gurel, B | |
dc.contributor.author | Clarke, M | |
dc.contributor.author | Atkin, M | |
dc.contributor.author | Chandler, R | |
dc.contributor.author | Messina, C | |
dc.contributor.author | Sumanasuriya, S | |
dc.contributor.author | Bianchini, D | |
dc.contributor.author | Barrero, M | |
dc.contributor.author | Petermolo, A | |
dc.contributor.author | Zafeiriou, Z | |
dc.contributor.author | Fontes, M | |
dc.contributor.author | Perez-Lopez, R | |
dc.contributor.author | Tunariu, N | |
dc.contributor.author | Fulton, B | |
dc.contributor.author | Jones, R | |
dc.contributor.author | McGovern, U | |
dc.contributor.author | Ralph, C | |
dc.contributor.author | Varughese, M | |
dc.contributor.author | Parikh, O | |
dc.contributor.author | Jain, S | |
dc.contributor.author | Elliott, T | |
dc.contributor.author | Sandhu, S | |
dc.contributor.author | Porta, N | |
dc.contributor.author | Hall, E | |
dc.contributor.author | Yuan, W | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | de Bono, JS | |
dc.date.accessioned | 2020-02-04T12:09:40Z | |
dc.date.issued | 2020-04-01 | |
dc.identifier.citation | The Journal of clinical investigation, 2020, 130 (4), pp. 1743 - 1751 | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3507 | |
dc.identifier.eissn | 1558-8238 | |
dc.identifier.doi | 10.1172/jci132031 | |
dc.description.abstract | The genomics of primary prostate cancer differ from those of metastatic castration-resistant prostate cancer (mCRPC). We studied genomic aberrations in primary prostate cancer biopsies from patients who developed mCRPC, also studying matching, same-patient, diagnostic, and mCRPC biopsies following treatment. We profiled 470 treatment-naive prostate cancer diagnostic biopsies and, for 61 cases, mCRPC biopsies, using targeted and low-pass whole-genome sequencing (n = 52). Descriptive statistics were used to summarize mutation and copy number profile. Prevalence was compared using Fisher's exact test. Survival correlations were studied using log-rank test. TP53 (27%) and PTEN (12%) and DDR gene defects (BRCA2 7%; CDK12 5%; ATM 4%) were commonly detected. TP53, BRCA2, and CDK12 mutations were markedly more common than described in the TCGA cohort. Patients with RB1 loss in the primary tumor had a worse prognosis. Among 61 men with matched hormone-naive and mCRPC biopsies, differences were identified in AR, TP53, RB1, and PI3K/AKT mutational status between same-patient samples. In conclusion, the genomics of diagnostic prostatic biopsies acquired from men who develop mCRPC differ from those of the nonlethal primary prostatic cancers. RB1/TP53/AR aberrations are enriched in later stages, but the prevalence of DDR defects in diagnostic samples is similar to mCRPC. | |
dc.format | Print | |
dc.format.extent | 1743 - 1751 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER SOC CLINICAL INVESTIGATION INC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Neoplasm Proteins | |
dc.subject | Biopsy | |
dc.subject | Disease-Free Survival | |
dc.subject | Survival Rate | |
dc.subject | Gene Expression Profiling | |
dc.subject | Genomics | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Male | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.title | Genomics of lethal prostate cancer at diagnosis and castration resistance. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-12-18 | |
rioxxterms.versionofrecord | 10.1172/jci132031 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | The Journal of clinical investigation | |
pubs.issue | 4 | |
pubs.notes | Not 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/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/ICR-CTSU Urology and Head and Neck Trials Team | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
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/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/ICR-CTSU Urology and Head and Neck Trials Team | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
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-status | Published | |
pubs.volume | 130 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Clinical Trials & Statistics Unit | |
icr.researchteam | ICR-CTSU Urology and Head and Neck Trials Team | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
dc.contributor.icrauthor | Seed, George | |
dc.contributor.icrauthor | Rescigno, Pasquale | |
dc.contributor.icrauthor | Miranda, Susana | |
dc.contributor.icrauthor | Gurel, Bora | |
dc.contributor.icrauthor | Clarke, Matthew | |
dc.contributor.icrauthor | Sumanasuriya, Semini | |
dc.contributor.icrauthor | Porta, Nuria | |
dc.contributor.icrauthor | Hall, Emma | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | De Bono, Johann | |