{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:35:32Z","timestamp":1778254532242,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","award":["C8594\/A23804"],"award-info":[{"award-number":["C8594\/A23804"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000289","name":"Blood Cancer UK","doi-asserted-by":"publisher","award":["CRCPSC-Dec21\\100002"],"award-info":[{"award-number":["CRCPSC-Dec21\\100002"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sir Bobby Robson Foundation, Little Princess Trust","award":["CCLGA 2016 08"],"award-info":[{"award-number":["CCLGA 2016 08"]}]},{"name":"Children\u2019s Cancer North, a CR UK Centre","award":["CTRQQR-2021\\100003"],"award-info":[{"award-number":["CTRQQR-2021\\100003"]}]},{"name":"Action Medical Research\/Great Ormond Street Hospital Charity","award":["GN2390"],"award-info":[{"award-number":["GN2390"]}]},{"name":"Horizon Europe-Mission Cancer THRIVE","award":["101136622"],"award-info":[{"award-number":["101136622"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuroblastoma (NB) is an aggressive childhood cancer requiring intensive multimodal therapies in high-risk (HRNB) patients. Currently, invasive surgical biopsies are required to classify NB risk group and assign treatment based on the tumour genetic profile. Circulating tumour DNA (ctDNA) obtained from blood samples can be used to identify tumour biomarkers. Here we applied targeted next-generation sequencing (tNGS) using a panel of 42 genes to analyse 32 NB ctDNA samples for the presence of single-nucleotide variants and copy number changes from 28 patients in all NB risk groups. In two additional ctDNA samples, droplet digital PCR was used to detect hotspot ALK variants. Pathogenic mutations with a variant allele frequency (VAF) &gt; 1% were identified in 13\/32 (41%) ctDNA samples. ALK and PTPN11 were the most frequent, each being detected in 4\/32 (13%) samples, together with oncogene amplifications. Targeted NGS of ctDNA detected actionable variants, including those absent in the diagnostic primary tumour due to spatial and temporal heterogeneity. Our findings confirm the usefulness of ctDNA in detecting genetic abnormalities in NB.<\/jats:p>","DOI":"10.3390\/ijms26199466","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T10:54:48Z","timestamp":1759229688000},"page":"9466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Detection of Targetable Genetic Abnormalities in Neuroblastoma Circulating Tumour DNA"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1227-8674","authenticated-orcid":false,"given":"Marina","family":"Danilenko","sequence":"first","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational & Clinical Research Institute, Newcastle University Centre for Cancer, Herschel Building, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-8530","authenticated-orcid":false,"given":"Sharanya","family":"Nath","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational & Clinical Research Institute, Newcastle University Centre for Cancer, Herschel Building, Newcastle upon Tyne NE1 7RU, UK"},{"name":"Newcastle Genetics Lab., Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4EP, UK"},{"name":"Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53726, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8593-3998","authenticated-orcid":false,"given":"Jack","family":"Baines","sequence":"additional","affiliation":[{"name":"Newcastle Genetics Lab., Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4EP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Freya","family":"Gordon","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational & Clinical Research Institute, Newcastle University Centre for Cancer, Herschel Building, Newcastle upon Tyne NE1 7RU, UK"},{"name":"Childhood Brain Tumour Research Group, Developmental Biology and Cancer, Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swathi","family":"Merugu","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational & Clinical Research Institute, Newcastle University Centre for Cancer, Herschel Building, Newcastle upon Tyne NE1 7RU, UK"},{"name":"The Immune Monitoring Facility, Ludwig Centre for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8957-6609","authenticated-orcid":false,"given":"Lisa M.","family":"Allinson","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational & Clinical Research Institute, Newcastle University Centre for Cancer, Herschel Building, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Potts","sequence":"additional","affiliation":[{"name":"Newcastle Genetics Lab., Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4EP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany","family":"Collins","sequence":"additional","affiliation":[{"name":"Newcastle Genetics Lab., Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4EP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3010-5757","authenticated-orcid":false,"given":"Angharad","family":"Goodman","sequence":"additional","affiliation":[{"name":"Newcastle Genetics Lab., Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4EP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel E.","family":"Kidman","sequence":"additional","affiliation":[{"name":"Newcastle Genetics Lab., Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4EP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciaron","family":"McAnulty","sequence":"additional","affiliation":[{"name":"Newcastle Genetics Lab., Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne NE1 4EP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3064-6713","authenticated-orcid":false,"given":"David","family":"Jamieson","sequence":"additional","affiliation":[{"name":"Translational & Clinical Research Institute, Newcastle University Centre for Cancer, Paul O\u2019Gorman Building, Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2208-3970","authenticated-orcid":false,"given":"Deborah A.","family":"Tweddle","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational & Clinical Research Institute, Newcastle University Centre for Cancer, Herschel Building, Newcastle upon Tyne NE1 7RU, UK"},{"name":"Department of Paediatric Oncology, Great North Children\u2019s Hospital, Newcastle NE1 4LP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s00441-018-2821-2","article-title":"Neuroblastoma: Clinical and biological approach to risk stratification and treatment","volume":"372","author":"Tolbert","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16078","DOI":"10.1038\/nrdp.2016.78","article-title":"Neuroblastoma","volume":"2","author":"Matthay","year":"2016","journal-title":"Nat. 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