{"doi":"10.3390/cancers13061282","title":"Establishing the Clinical Utility of ctDNA Analysis for Diagnosis, Prognosis, and Treatment Monitoring of Retinoblastoma: The Aqueous Humor Liquid Biopsy","abstract":"Because direct tumor biopsy is prohibited for retinoblastoma (RB), eye-specific molecular biomarkers are not used in clinical practice for RB. Recently, we demonstrated that the aqueous humor (AH) is a rich liquid biopsy source of cell-free tumor DNA. Herein, we detail clinically-relevant molecular biomarkers from the first year of prospective validation data. Seven eyes from 6 RB patients who had AH sampled at diagnosis and throughout therapy with ≥12 months of follow-up were included. Cell-free DNA (cfDNA) from each sample was isolated and sequenced to assess genome-wide somatic copy number alterations (SCNAs), followed by targeted resequencing for pathogenic variants using a RB1 and MYCN custom hybridization panel. Tumoral genomic information was detected in 100% of diagnostic AH samples. Of the seven diagnostic AH samples, 5/7 were positive for RB SCNAs. Mutational analysis identified RB1 variants in 5/7 AH samples, including the 2 samples in which no SCNAs were detected. Two eyes failed therapy and required enucleation; both had poor prognostic biomarkers (chromosome 6p gain or MYCN amplification) present in the AH at the time of diagnosis. In the context of previously established pre-analytical, analytical, and clinical validity, this provides evidence for larger, prospective studies to further establish the clinical utility of the AH liquid biopsy and its applications to precision oncology for RB.","journal":"Cancers","year":2021,"id":153854,"datarank":0.6307038929086449,"base_score":4.204692619390966,"endowment":4.204692619390966,"self_citation_contribution":0.6307038929086449,"citation_network_contribution":0.0,"self_endowment_contribution":0.6307038929086449,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":66,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"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":652125,"name":"Mary E. Kim","orcid":"0000-0002-7986-6119","position":1,"is_corresponding":false},{"id":317488,"name":"Ashley Polski","orcid":"0000-0001-6301-6892","position":2,"is_corresponding":false},{"id":317489,"name":"Rishvanth K. Prabakar","orcid":"0000-0002-2377-1567","position":3,"is_corresponding":false},{"id":249285,"name":"Li Shen","orcid":"0000-0002-0436-0199","position":4,"is_corresponding":false},{"id":652126,"name":"Chen‐Ching Peng","orcid":"0000-0002-2703-1275","position":5,"is_corresponding":false},{"id":317490,"name":"Mark W. Reid","orcid":"0000-0002-1942-225X","position":6,"is_corresponding":false},{"id":317491,"name":"Patricia Chévez‐Barrios","orcid":"0000-0001-6275-2660","position":7,"is_corresponding":false},{"id":317493,"name":"Jonathan W. Kim","orcid":"0000-0001-5860-2192","position":8,"is_corresponding":false},{"id":488377,"name":"Rachana Shah","orcid":"0000-0002-8445-2172","position":9,"is_corresponding":false},{"id":317492,"name":"Rima Jubran","orcid":"0000-0002-2169-7826","position":10,"is_corresponding":false},{"id":317494,"name":"Peter Kühn","orcid":"0000-0003-2629-4505","position":11,"is_corresponding":false},{"id":317495,"name":"David Cobrinik","orcid":"0000-0002-4478-2417","position":12,"is_corresponding":false},{"id":383468,"name":"Jaclyn A. Biegel","orcid":"0000-0001-9270-6411","position":13,"is_corresponding":false},{"id":249294,"name":"Xiaowu Gai","orcid":"0000-0001-8679-9703","position":14,"is_corresponding":false},{"id":12670,"name":"James Hicks","orcid":"0000-0001-5353-4338","position":15,"is_corresponding":false},{"id":317496,"name":"Jesse L. Berry","orcid":"0000-0002-8907-9100","position":16,"is_corresponding":false},{"id":317487,"name":"Liya Xu","orcid":"0000-0002-5501-2039","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:43:44.759273Z","pmid":"33805776","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":[]}