dc.contributor.author | Stankunaite, R | |
dc.contributor.author | George, SL | |
dc.contributor.author | Gallagher, L | |
dc.contributor.author | Jamal, S | |
dc.contributor.author | Shaikh, R | |
dc.contributor.author | Yuan, L | |
dc.contributor.author | Hughes, D | |
dc.contributor.author | Proszek, PZ | |
dc.contributor.author | Carter, P | |
dc.contributor.author | Pietka, G | |
dc.contributor.author | Heide, T | |
dc.contributor.author | James, C | |
dc.contributor.author | Tari, H | |
dc.contributor.author | Lynn, C | |
dc.contributor.author | Jain, N | |
dc.contributor.author | Portela, LR | |
dc.contributor.author | Rogers, T | |
dc.contributor.author | Vaidya, SJ | |
dc.contributor.author | Chisholm, JC | |
dc.contributor.author | Carceller, F | |
dc.contributor.author | Szychot, E | |
dc.contributor.author | Mandeville, H | |
dc.contributor.author | Angelini, P | |
dc.contributor.author | Jesudason, AB | |
dc.contributor.author | Jackson, M | |
dc.contributor.author | Marshall, LV | |
dc.contributor.author | Gatz, SA | |
dc.contributor.author | Anderson, J | |
dc.contributor.author | Sottoriva, A | |
dc.contributor.author | Chesler, L | |
dc.contributor.author | Hubank, M | |
dc.date.accessioned | 2022-01-06T14:41:29Z | |
dc.date.available | 2022-01-06T14:41:29Z | |
dc.date.issued | 2021-12-18 | |
dc.identifier.citation | European journal of cancer (Oxford, England : 1990), 2021 | |
dc.identifier.issn | 0959-8049 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4936 | |
dc.identifier.eissn | 1879-0852 | |
dc.identifier.doi | 10.1016/j.ejca.2021.09.042 | |
dc.description.abstract | OBJECTIVE: Clinical diagnostic sequencing of circulating tumour DNA (ctDNA) is well advanced for adult patients, but application to paediatric cancer patients lags behind. METHODS: To address this, we have developed a clinically relevant (67 gene) NGS capture panel and accompanying workflow that enables sensitive and reliable detection of low-frequency genetic variants in cell-free DNA (cfDNA) from children with solid tumours. We combined gene panel sequencing with low pass whole-genome sequencing of the same library to inform on genome-wide copy number changes in the blood. RESULTS: Analytical validity was evaluated using control materials, and the method was found to be highly sensitive (0.96 for SNVs and 0.97 for INDEL), specific (0.82 for SNVs and 0.978 for INDEL), repeatable (>0.93 [95% CI: 0.89-0.95]) and reproducible (>0.87 [95% CI: 0.87-0.95]). Potential for clinical application was demonstrated in 39 childhood cancer patients with a spectrum of solid tumours in which the single nucleotide variants expected from tumour sequencing were detected in cfDNA in 94.4% (17/18) of cases with active extracranial disease. In 13 patients, where serial samples were available, we show a close correlation between events detected in cfDNA and treatment response, demonstrate that cfDNA analysis could be a useful tool to monitor disease progression, and show cfDNA sequencing has the potential to identify targetable variants that were not detected in tumour samples. CONCLUSIONS: This is the first pan-cancer DNA sequencing panel that we know to be optimised for cfDNA in children for blood-based molecular diagnostics in paediatric solid tumours. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCI LTD | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.title | Circulating tumour DNA sequencing to determine therapeutic response and identify tumour heterogeneity in patients with paediatric solid tumours. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-09-28 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.ejca.2021.09.042 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2021-12-18 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | European journal of cancer (Oxford, England : 1990) | |
pubs.notes | No embargo | |
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/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics | |
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/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials in Children and Young People | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Sarcoma Clinical Trials in Children and Young People/Sarcoma Clinical Trials in Children and Young People (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Clinical Trials in children and young people | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Clinical Trials in children and young people/Sarcoma Clinical Trials in Children and Young People (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Paediatric and Adolescent Radiotherapy | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/14/15 Starting Cohort | |
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/Students/PhD and MPhil/20/21 Starting Cohort | |
pubs.publication-status | Published | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Cancer Biomarkers | |
icr.researchteam | Evolutionary Genomics & Modelling | |
icr.researchteam | Paediatric Solid Tumour Biology and Therapeutics | |
icr.researchteam | Sarcoma Clinical Trials in children and young people | |
icr.researchteam | Translational Genomics | |
icr.researchteam | Paediatric and Adolescent Radiotherapy | |
dc.contributor.icrauthor | Stankunaite, Reda | |
dc.contributor.icrauthor | George, Sally | |
dc.contributor.icrauthor | Gallagher, Lewis | |
dc.contributor.icrauthor | Hughes, Deborah | |
dc.contributor.icrauthor | Heide, Timon | |
dc.contributor.icrauthor | James, Chela | |
dc.contributor.icrauthor | Tari, Haider | |
dc.contributor.icrauthor | Rogers, Anthony | |
dc.contributor.icrauthor | Angelini, Paola | |
dc.contributor.icrauthor | Sottoriva, Andrea | |
dc.contributor.icrauthor | Chesler, Louis | |