{"doi":"10.1172/jci.insight.156529","title":"Circulating cell-free methylated DNA reveals tissue-specific, cellular damage from radiation treatment","abstract":"Radiation therapy is an effective cancer treatment, although damage to healthy tissues is common. Here we analyzed cell-free, methylated DNA released from dying cells into the circulation to evaluate radiation-induced cellular damage in different tissues. To map the circulating DNA fragments to human and mouse tissues, we established sequencing-based, cell-type-specific reference DNA methylation atlases. We found that cell-type-specific DNA blocks were mostly hypomethylated and located within signature genes of cellular identity. Cell-free DNA fragments were captured from serum samples by hybridization to CpG-rich DNA panels and mapped to the DNA methylation atlases. In a mouse model, thoracic radiation-induced tissue damage was reflected by dose-dependent increases in lung endothelial and cardiomyocyte methylated DNA in serum. The analysis of serum samples from patients with breast cancer undergoing radiation treatment revealed distinct dose-dependent and tissue-specific epithelial and endothelial responses to radiation across multiple organs. Strikingly, patients treated for right-sided breast cancers also showed increased hepatocyte and liver endothelial DNA in the circulation, indicating the impact on liver tissues. Thus, changes in cell-free methylated DNA can uncover cell-type-specific effects of radiation and provide a readout of the biologically effective radiation dose received by healthy tissues.","journal":"JCI Insight","year":2023,"id":339839,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9279,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":662150,"name":"Netanel Loyfer","orcid":"0000-0002-2537-3132","position":1,"is_corresponding":false},{"id":368338,"name":"Amber J. Kiliti","orcid":"0000-0002-8581-6222","position":2,"is_corresponding":false},{"id":568554,"name":"Marcel O. Schmidt","orcid":"0000-0002-3991-2766","position":3,"is_corresponding":false},{"id":992295,"name":"Sapir Shabi-Porat","orcid":null,"position":4,"is_corresponding":false},{"id":561759,"name":"Sidharth Jain","orcid":"0000-0002-6263-651X","position":5,"is_corresponding":false},{"id":793279,"name":"Sarah Martinez","orcid":"0000-0001-9528-7152","position":6,"is_corresponding":false},{"id":662151,"name":"A. Patrick McDeed","orcid":"0000-0003-3380-4112","position":7,"is_corresponding":false},{"id":991994,"name":"Nesreen Shahrour","orcid":"0000-0001-9446-783X","position":8,"is_corresponding":false},{"id":494773,"name":"Elizabeth Ballew","orcid":null,"position":9,"is_corresponding":false},{"id":514226,"name":"Yun‐Tien Lin","orcid":null,"position":10,"is_corresponding":false},{"id":513540,"name":"Heng‐Hong Li","orcid":"0000-0001-5979-5141","position":11,"is_corresponding":false},{"id":4261,"name":"Anne Deslattes Mays","orcid":"0000-0001-7951-3439","position":12,"is_corresponding":false},{"id":992296,"name":"Sonali Rudra","orcid":null,"position":13,"is_corresponding":false},{"id":394721,"name":"Anna T. Riegel","orcid":"0000-0001-6585-8612","position":14,"is_corresponding":false},{"id":494771,"name":"Keith Unger","orcid":null,"position":15,"is_corresponding":false},{"id":39694,"name":"Tommy Kaplan","orcid":"0000-0002-1892-5461","position":16,"is_corresponding":false},{"id":288143,"name":"Anton Wellstein","orcid":"0000-0002-0570-4950","position":17,"is_corresponding":false},{"id":1073817,"name":"Megan E. McNamara","orcid":"0000-0002-2591-0567","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:10:49.535464Z","pmid":"37318863","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":[]}