دورية أكاديمية
Molecular Characterization of Circulating Tumor DNA in Pediatric Rhabdomyosarcoma: A Feasibility Study.
| العنوان: | Molecular Characterization of Circulating Tumor DNA in Pediatric Rhabdomyosarcoma: A Feasibility Study. |
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| المؤلفون: | Ruhen, O, Lak, NSM, Stutterheim, J, Danielli, SG, Chicard, M, Iddir, Y, Saint-Charles, A, Di Paolo, V, Tombolan, L, Gatz, SA, Aladowicz, E, Proszek, P, Jamal, S, Stankunaite, R, Hughes, D, Carter, P, Izquierdo, E, Wasti, A, Chisholm, JC, George, SL, Pace, E, Chesler, L, Aerts, I, Pierron, G, Zaidi, S, Delattre, O, Surdez, D, Kelsey, A, Hubank, M, Bonvini, P, Bisogno, G, Di Giannatale, A, Schleiermacher, G, Schäfer, BW, Tytgat, GAM, Shipley, J |
| المساهمون: | Stankunaite, Reda, Wasti, Ajla, George, Sally, Chesler, Louis, Shipley, Janet |
| بيانات النشر: | LIPPINCOTT WILLIAMS & WILKINS |
| سنة النشر: | 2022 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | Humans, Child, Mice, Animals, Circulating Tumor DNA, Feasibility Studies, Prospective Studies, Biomarkers, Tumor, Mutation, Neoplasms, Rhabdomyosarcoma, Embryonal |
| جغرافية الموضوع: | United States |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print; application/pdf |
| اللغة: | English |
| تدمد: | 2473-4284 |
| العلاقة: | JCO Precision Oncology, 2022, 6 (6), pp. e2100534 -; https://repository.icr.ac.uk/handle/internal/5614Test |
| DOI: | 10.1200/PO.21.00534 |
| الإتاحة: | https://doi.org/10.1200/PO.21.00534Test https://repository.icr.ac.uk/handle/internal/5614Test |
| حقوق: | https://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.21DD47D5 |
| قاعدة البيانات: | BASE |
| تدمد: | 24734284 |
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| DOI: | 10.1200/PO.21.00534 |