dc.contributor.author | Ruhen, O | |
dc.contributor.author | Lak, NSM | |
dc.contributor.author | Stutterheim, J | |
dc.contributor.author | Danielli, SG | |
dc.contributor.author | Chicard, M | |
dc.contributor.author | Iddir, Y | |
dc.contributor.author | Saint-Charles, A | |
dc.contributor.author | Di Paolo, V | |
dc.contributor.author | Tombolan, L | |
dc.contributor.author | Gatz, SA | |
dc.contributor.author | Aladowicz, E | |
dc.contributor.author | Proszek, P | |
dc.contributor.author | Jamal, S | |
dc.contributor.author | Stankunaite, R | |
dc.contributor.author | Hughes, D | |
dc.contributor.author | Carter, P | |
dc.contributor.author | Izquierdo, E | |
dc.contributor.author | Wasti, A | |
dc.contributor.author | Chisholm, JC | |
dc.contributor.author | George, SL | |
dc.contributor.author | Pace, E | |
dc.contributor.author | Chesler, L | |
dc.contributor.author | Aerts, I | |
dc.contributor.author | Pierron, G | |
dc.contributor.author | Zaidi, S | |
dc.contributor.author | Delattre, O | |
dc.contributor.author | Surdez, D | |
dc.contributor.author | Kelsey, A | |
dc.contributor.author | Hubank, M | |
dc.contributor.author | Bonvini, P | |
dc.contributor.author | Bisogno, G | |
dc.contributor.author | Di Giannatale, A | |
dc.contributor.author | Schleiermacher, G | |
dc.contributor.author | Schäfer, BW | |
dc.contributor.author | Tytgat, GAM | |
dc.contributor.author | Shipley, J | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2022-12-22T12:08:13Z | |
dc.date.available | 2022-12-22T12:08:13Z | |
dc.date.issued | 2022-10-01 | |
dc.identifier.citation | JCO Precision Oncology, 2022, 6 (6), pp. e2100534 - | |
dc.identifier.issn | 2473-4284 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5614 | |
dc.identifier.eissn | 2473-4284 | |
dc.identifier.eissn | 2473-4284 | |
dc.identifier.doi | 10.1200/PO.21.00534 | |
dc.description.abstract | PURPOSE: Rhabdomyosarcomas (RMS) are rare neoplasms affecting children and young adults. Efforts to improve patient survival have been undermined by a lack of suitable disease markers. Plasma circulating tumor DNA (ctDNA) has shown promise as a potential minimally invasive biomarker and monitoring tool in other cancers; however, it remains underexplored in RMS. We aimed to determine the feasibility of identifying and quantifying ctDNA in plasma as a marker of disease burden and/or treatment response using blood samples from RMS mouse models and patients. METHODS: We established mouse models of RMS and applied quantitative polymerase chain reaction (PCR) and droplet digital PCR (ddPCR) to detect ctDNA within the mouse plasma. Potential driver mutations, copy-number alterations, and DNA breakpoints associated with PAX3/7-FOXO1 gene fusions were identified in the RMS samples collected at diagnosis. Patient-matched plasma samples collected from 28 patients with RMS before, during, and after treatment were analyzed for the presence of ctDNA via ddPCR, panel sequencing, and/or whole-exome sequencing. RESULTS: Human tumor-derived DNA was detectable in plasma samples from mouse models of RMS and correlated with tumor burden. In patients, ctDNA was detected in 14/18 pretreatment plasma samples with ddPCR and 7/7 cases assessed by sequencing. Levels of ctDNA at diagnosis were significantly higher in patients with unfavorable tumor sites, positive nodal status, and metastasis. In patients with serial plasma samples (n = 18), fluctuations in ctDNA levels corresponded to treatment response. CONCLUSION: Comprehensive ctDNA analysis combining high sensitivity and throughput can identify key molecular drivers in RMS models and patients, suggesting potential as a minimally invasive biomarker. Preclinical assessment of treatments using mouse models and further patient testing through prospective clinical trials are now warranted. | |
dc.format | Print | |
dc.format.extent | e2100534 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | |
dc.relation.ispartof | JCO Precision Oncology | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Humans | |
dc.subject | Child | |
dc.subject | Mice | |
dc.subject | Animals | |
dc.subject | Circulating Tumor DNA | |
dc.subject | Feasibility Studies | |
dc.subject | Prospective Studies | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Mutation | |
dc.subject | Neoplasms | |
dc.subject | Rhabdomyosarcoma, Embryonal | |
dc.title | Molecular Characterization of Circulating Tumor DNA in Pediatric Rhabdomyosarcoma: A Feasibility Study. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-08-26 | |
dc.date.updated | 2022-12-22T12:07:25Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1200/PO.21.00534 | |
rioxxterms.licenseref.startdate | 2022-10-01 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36265118 | |
pubs.issue | 6 | |
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/Paediatric Solid Tumour Biology and Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
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/Molecular Pathology | |
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 Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
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/Translational Genomics/Translational Genomics (hon.) | |
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/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.organisational-group | /ICR/Students/MD(Res) | |
pubs.organisational-group | /ICR/Students/MD(Res)/Starting Cohort 20/21 | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1200/po.21.00534 | |
pubs.volume | 6 | |
icr.researchteam | Paediatric Tumour Biology | |
icr.researchteam | Sarcoma Mol Pathol | |
dc.contributor.icrauthor | Stankunaite, Reda | |
dc.contributor.icrauthor | Wasti, Ajla | |
dc.contributor.icrauthor | George, Sally | |
dc.contributor.icrauthor | Chesler, Louis | |
dc.contributor.icrauthor | Shipley, Janet | |
icr.provenance | Deposited by Mr Arek Surman on 2022-12-22. Deposit type is initial. No. of files: 1. Files: Molecular Characterization of Circulating Tumor DNA in Pediatric Rhabdomyosarcoma A Feasibility Study.pdf | |