{"doi":"10.1016/j.jmoldx.2025.05.007","title":"Cell-Free DNA, Tumor Molecular Concordance, and Clinical Correlates of Patients with Cancer Treated in a Large Community Health Care Network","abstract":"Blood collection, plasma processing, and cell-free DNA (cfDNA) purification were optimized to capture circulating tumor DNA without blood cell background DNA among 874 patients with cancer. cfDNA comprised predominantly mononucleosomal fragments [n = 874; mean (x¯) ± SD = 166 ± 5 bp] that generated comparably sized sequencing reads (x¯ ± SD = 162 ± 25 bp). Despite a vast range of cfDNA concentrations (0.50 to 1132.9 ng/mL) across 21 tumor types, matched tumor and blood specimens (n = 430 patients) revealed high concordance for coding (median = 97%) and clinical oncogenic mutations (median = 88% concordance). Therapeutically actionable mutations were identified in 233 patients by both assays, whereas 126 patients had oncogenic mutations without an established pharmacotherapeutic agent. An additional 48 patients (11%) had actionable mutations detected only in cfDNA assays, whereas 23 patients (5%) had mutations in tumor only. Concordance was high in both prevalent (lung, breast, and colon) and rare tumors (appendiceal, sarcoma). Cell-free DNA levels from diagnostic blood specimens were a strong indicator of patient survival duration independent of age, sex, tumor type, and stage, demonstrative of a potentially important role as a prognostic biomarker. Mutations in established oncogenes and tumor suppressors were readily detectable across all tumor types in circulating tumor DNA, indicating a diagnostic role for cfDNA from blood extending beyond the identification of companion therapeutics to patient screening and monitoring.","journal":"Journal of Molecular Diagnostics","year":2025,"id":518525,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.5324,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1386422,"name":"Patti Petrosko","orcid":null,"position":1,"is_corresponding":false},{"id":1386423,"name":"Phillip H. 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