dc.contributor.author | Seed, G | |
dc.contributor.author | Yuan, W | |
dc.contributor.author | Mateo, J | |
dc.contributor.author | Carreira, S | |
dc.contributor.author | Bertan, C | |
dc.contributor.author | Lambros, M | |
dc.contributor.author | Boysen, G | |
dc.contributor.author | Ferraldeschi, R | |
dc.contributor.author | Miranda, S | |
dc.contributor.author | Figueiredo, I | |
dc.contributor.author | Riisnaes, R | |
dc.contributor.author | Crespo, M | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Talevich, E | |
dc.contributor.author | Robinson, DR | |
dc.contributor.author | Kunju, LP | |
dc.contributor.author | Wu, Y-M | |
dc.contributor.author | Lonigro, R | |
dc.contributor.author | Sandhu, S | |
dc.contributor.author | Chinnaiyan, AM | |
dc.contributor.author | de Bono, JS | |
dc.date.accessioned | 2017-08-14T13:45:35Z | |
dc.date.issued | 2017-10-15 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2017, 23 (20), pp. 6070 - 6077 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/772 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-17-0972 | |
dc.description.abstract | Purpose: Precise detection of copy number aberrations (CNA) from tumor biopsies is critically important to the treatment of metastatic prostate cancer. The use of targeted panel next-generation sequencing (NGS) is inexpensive, high throughput, and easily feasible, allowing single-nucleotide variant calls, but CNA estimation from this remains challenging.Experimental Design: We evaluated CNVkit for CNA identification from amplicon-based targeted NGS in a cohort of 110 fresh castration-resistant prostate cancer biopsies and used capture-based whole-exome sequencing (WES), array comparative genomic hybridization (aCGH), and FISH to explore the viability of this approach.Results: We showed that this method produced highly reproducible CNA results (r = 0.92), with the use of pooled germline DNA as a coverage reference supporting precise CNA estimation. CNA estimates from targeted NGS were comparable with WES (r = 0.86) and aCGH (r = 0.7); for key selected genes (BRCA2, MYC, PIK3CA, PTEN, and RB1), CNA estimation correlated well with WES (r = 0.91) and aCGH (r = 0.84) results. The frequency of CNAs in our population was comparable with that previously described (i.e., deep deletions: BRCA2 4.5%; RB1 8.2%; PTEN 15.5%; amplification: AR 45.5%; gain: MYC 31.8%). We also showed, utilizing FISH, that CNA estimation can be impacted by intratumor heterogeneity and demonstrated that tumor microdissection allows NGS to provide more precise CNA estimates.Conclusions: Targeted NGS and CNVkit-based analyses provide a robust, precise, high-throughput, and cost-effective method for CNA estimation for the delivery of more precise patient care. Clin Cancer Res; 23(20); 6070-7. ©2017 AACR. | |
dc.format | Print-Electronic | |
dc.format.extent | 6070 - 6077 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Humans | |
dc.subject | Prostatic Neoplasms | |
dc.subject | BRCA2 Protein | |
dc.subject | Biopsy | |
dc.subject | Reproducibility of Results | |
dc.subject | Computational Biology | |
dc.subject | Genetic Heterogeneity | |
dc.subject | Male | |
dc.subject | Comparative Genomic Hybridization | |
dc.subject | DNA Copy Number Variations | |
dc.subject | High-Throughput Nucleotide Sequencing | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Whole Exome Sequencing | |
dc.title | Gene Copy Number Estimation from Targeted Next-Generation Sequencing of Prostate Cancer Biopsies: Analytic Validation and Clinical Qualification. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-07-19 | |
rioxxterms.funder | The Institute of Cancer Research | |
rioxxterms.identifier.project | Unspecified | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-17-0972 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2017-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.issue | 20 | |
pubs.notes | 12 months | |
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/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/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 | 23 | |
pubs.embargo.terms | 12 months | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
dc.contributor.icrauthor | Seed, George | |
dc.contributor.icrauthor | Carreira, Suzanne | |
dc.contributor.icrauthor | Miranda, Susana | |
dc.contributor.icrauthor | De Bono, Johann | |