{"doi":"10.1016/j.neo.2021.06.005","title":"Detection of circulating tumor DNA without a tumor-informed search using next-generation sequencing is a prognostic biomarker in pancreatic ductal adenocarcinoma","abstract":"The confounding effects of next-generation sequencing (NGS) noise on detection of low frequency circulating tumor DNA (ctDNA) without a priori knowledge of solid tumor mutations has limited the applications of circulating cell-free DNA (ccfDNA) in clinical oncology . Here, we use a 118 gene panel and leverage ccfDNA technical replicates to eliminate NGS-associated errors while also enhancing detection of ctDNA from pancreatic ductal adenocarcinomas (PDACs). Pre-operative ccfDNA and tumor DNA were acquired from 14 patients with PDAC (78.6% stage II-III). Post-operative ccfDNA was also collected from 11 of the patients within 100 days of surgery . ctDNA detection was restricted to variants corresponding to pathogenic mutations in PDAC present in both replicates. PDAC-associated pathogenic mutations were detected in pre-operative ccfDNA in four genes ( KRAS , TP53, SMAD4, ALK ) from five patients. Of the nine ctDNA variants detected (variant allele frequency: 0.08%-1.59%), five had a corresponding mutation in tumor DNA. Pre-operative detection of ctDNA was associated with shorter survival (312 vs. 826 days; χ 2 =5.4, P = 0.021). Guiding ctDNA detection in pre-operative ccfDNA based on mutations present in tumor DNA yielded a similar survival analysis. Detection of ctDNA in the post-operative ccfDNA with or without tumor-informed guidance was not associated with outcomes. Therefore, the detection of PDAC-derived ctDNA during a broad and untargeted survey of ccfDNA with NGS may be a valuable, non-invasive, prognostic biomarker to integrate into the clinical assessment and management of patients prior to surgery.","journal":"Neoplasia","year":2021,"id":182819,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":419495,"name":"Sabine Hellwig","orcid":"0000-0002-9809-947X","position":1,"is_corresponding":false},{"id":4465,"name":"David  A. Nix","orcid":"0009-0002-3383-8582","position":2,"is_corresponding":false},{"id":258889,"name":"Mary P. Bronner","orcid":"0000-0001-5574-4072","position":3,"is_corresponding":false},{"id":361080,"name":"Alun Thomas","orcid":"0000-0001-5650-7044","position":4,"is_corresponding":false},{"id":419496,"name":"Carrie L. Fuertes","orcid":"0000-0003-2477-0328","position":5,"is_corresponding":false},{"id":420980,"name":"Cindy Hamil","orcid":null,"position":6,"is_corresponding":false},{"id":337606,"name":"Ignacio Garrido‐Laguna","orcid":"0000-0003-2273-9028","position":7,"is_corresponding":false},{"id":400530,"name":"Courtney L. Scaife","orcid":"0000-0003-2497-4961","position":8,"is_corresponding":false},{"id":735361,"name":"Sean J. Mulvihill","orcid":"0000-0002-0078-8980","position":9,"is_corresponding":false},{"id":68989,"name":"Hunter R. Underhill","orcid":"0000-0002-7389-1487","position":10,"is_corresponding":false},{"id":735360,"name":"Kajsa E. Affolter","orcid":"0000-0002-1703-0535","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T23:48:13.605421Z","pmid":"34298235","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":[]}