{"doi":"10.1093/neuonc/noab299","title":"Liquid biopsy detection of genomic alterations in pediatric brain tumors from cell-free DNA in peripheral blood, CSF, and urine","abstract":"BACKGROUND: The ability to identify genetic alterations in cancers is essential for precision medicine; however, surgical approaches to obtain brain tumor tissue are invasive. Profiling circulating tumor DNA (ctDNA) in liquid biopsies has emerged as a promising approach to avoid invasive procedures. Here, we systematically evaluated the feasibility of profiling pediatric brain tumors using ctDNA obtained from plasma, cerebrospinal fluid (CSF), and urine. METHODS: We prospectively collected 564 specimens (257 blood, 240 urine, and 67 CSF samples) from 258 patients across all histopathologies. We performed ultra-low-pass whole-genome sequencing (ULP-WGS) to assess copy number variations and estimate tumor fraction and developed a pediatric CNS tumor hybrid capture panel for deep sequencing of specific mutations and fusions. RESULTS: ULP-WGS detected copy number alterations in 9/46 (20%) CSF, 3/230 (1.3%) plasma, and 0/153 urine samples. Sequencing detected alterations in 3/10 (30%) CSF, 2/74 (2.7%) plasma, and 0/2 urine samples. The only positive results were in high-grade tumors. However, most samples had insufficient somatic mutations (median 1, range 0-39) discoverable by the sequencing panel to provide sufficient power to detect tumor fractions of greater than 0.1%. CONCLUSIONS: Children with brain tumors harbor very low levels of ctDNA in blood, CSF, and urine, with CSF having the most DNA detectable. Molecular profiling is feasible in a small subset of high-grade tumors. The level of clonal aberrations per genome is low in most of the tumors, posing a challenge for detection using whole-genome or even targeted sequencing methods. Substantial challenges therefore remain to genetically characterize pediatric brain tumors from liquid biopsies.","journal":"Neuro-Oncology","year":2022,"id":234990,"datarank":3.1023571240936354,"base_score":4.477336814478207,"endowment":4.477336814478207,"self_citation_contribution":0.6716005221717312,"citation_network_contribution":2.4307566019219045,"self_endowment_contribution":0.6716005221717312,"citer_contribution":2.4307566019219045,"corpus_percentile":null,"corpus_rank":null,"citation_count":87,"citer_count":87,"citers_with_citation_signal":68,"citers_with_endowment":68,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":38077,"name":"Denisse Rotem","orcid":"0000-0001-5030-5919","position":1,"is_corresponding":false},{"id":38075,"name":"Gregory Gydush","orcid":null,"position":2,"is_corresponding":false},{"id":38079,"name":"Sarah C. Reed","orcid":"0000-0003-2191-6643","position":3,"is_corresponding":false},{"id":38076,"name":"Justin Rhoades","orcid":"0000-0002-0630-908X","position":4,"is_corresponding":false},{"id":13516,"name":"Gavin Ha","orcid":"0000-0001-7578-7272","position":5,"is_corresponding":false},{"id":75583,"name":"Christopher Lo","orcid":"0000-0003-2171-6254","position":6,"is_corresponding":false},{"id":805873,"name":"Mark Fleharty","orcid":"0000-0002-8141-8091","position":7,"is_corresponding":false},{"id":805875,"name":"Madeleine Duran","orcid":"0000-0003-1648-2369","position":8,"is_corresponding":false},{"id":1402,"name":"Robert T. Jones","orcid":"0000-0001-8007-4023","position":9,"is_corresponding":false},{"id":1375,"name":"Sarah Becker","orcid":null,"position":10,"is_corresponding":false},{"id":852376,"name":"Michaela J. Haller","orcid":null,"position":11,"is_corresponding":false},{"id":1377,"name":"Claire Sinai","orcid":"0000-0002-7872-0951","position":12,"is_corresponding":false},{"id":1395,"name":"Liliana Goumnerova","orcid":"0000-0002-2662-719X","position":13,"is_corresponding":false},{"id":16671,"name":"Todd R. Golub","orcid":"0000-0003-0113-2403","position":14,"is_corresponding":false},{"id":63891,"name":"John Christopher Love","orcid":"0000-0003-0921-3144","position":15,"is_corresponding":false},{"id":1412,"name":"Keith L. Ligon","orcid":"0000-0002-7733-600X","position":16,"is_corresponding":false},{"id":18801,"name":"Karen Wright","orcid":"0000-0002-9578-1545","position":17,"is_corresponding":false},{"id":38080,"name":"Viktor A. Adalsteinsson","orcid":"0000-0003-4555-2485","position":18,"is_corresponding":false},{"id":1398,"name":"Rameen Beroukhim","orcid":"0000-0001-6303-3609","position":19,"is_corresponding":false},{"id":1399,"name":"Pratiti Bandopadhayay","orcid":"0000-0002-4175-4760","position":20,"is_corresponding":false},{"id":261435,"name":"Mélanie Pagès","orcid":null,"position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:21:42.662304Z","pmid":"34984433","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}