{"doi":"10.3390/cancers17121962","title":"DNA Damage Repair Pathway Alterations and Immune Landscape Differences in Pediatric/Adolescent, Young Adult (AYA) and Adult Sarcomas","abstract":"Background: DNA damage response (DDR) pathway alterations contribute to genomic instability and malignant progression in several cancers. Methods: We retrospectively reviewed molecular profiles from 5309 sarcoma patient samples, including 746 from pediatric/adolescent and young adults (ped/AYA), encompassing 38 histologic subtypes. The gene expression profiles were further analyzed for immunotherapy-related biomarker associations, including analysis of the T cell-inflamed score. Results: Pathogenic/likely pathogenic DDR alterations were detected in 15.9% (N = 842) of samples overall and 9.25% (N = 69) of Ped/AYA tumors, with mutations occurring most frequently in ATRX (10.1%). Shorter overall survival was observed for patients with DDR-alterations compared to those with DDR-wildtype tumors (Hazard Ratio = 1.172, 95% CI: 1.068–1.287; p < 0.001). In many subtypes, DDR-mutated tumors were found to have increased rates of immune markers, including PD-L1+, dMMR/MSI-high, and TMB. Conclusions: Our study of somatic DDR-pathway mutations provides a better understanding of the molecular associations across sarcoma subtypes that may aid in developing future prognostic and therapeutic options for these rare cancers.","journal":"Cancers","year":2025,"id":539593,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7916,"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":1053011,"name":"Andrew Elliott","orcid":"0000-0001-8494-8031","position":1,"is_corresponding":false},{"id":1426634,"name":"Steven Bialick","orcid":"0000-0003-0833-1034","position":2,"is_corresponding":false},{"id":260066,"name":"César Serrano","orcid":"0000-0003-1416-8739","position":3,"is_corresponding":false},{"id":512174,"name":"Margaret von Mehren","orcid":"0000-0001-6158-890X","position":4,"is_corresponding":false},{"id":19999,"name":"Matthew J. Oberley","orcid":"0000-0001-6419-2513","position":5,"is_corresponding":false},{"id":793074,"name":"Andrea P. Espejo Freire","orcid":"0000-0001-9903-0864","position":6,"is_corresponding":false},{"id":582114,"name":"Priscila Barreto Coelho","orcid":null,"position":7,"is_corresponding":false},{"id":793071,"name":"Philippos Apolinário Costa","orcid":"0000-0001-9681-0515","position":8,"is_corresponding":false},{"id":793078,"name":"Gina Z. D’Amato","orcid":"0000-0001-6981-7527","position":9,"is_corresponding":false},{"id":793076,"name":"Emily Jonczak","orcid":"0000-0002-0983-8016","position":10,"is_corresponding":false},{"id":260070,"name":"Jonathan C. Trent","orcid":"0000-0001-6169-5238","position":11,"is_corresponding":false},{"id":713243,"name":"Elizabeth A. Montgomery","orcid":"0000-0001-9788-8218","position":12,"is_corresponding":false},{"id":23524,"name":"David B. Lombard","orcid":"0000-0002-4292-0185","position":13,"is_corresponding":false},{"id":957832,"name":"Andrew E. Rosenberg","orcid":"0000-0002-4536-8824","position":14,"is_corresponding":false},{"id":1293438,"name":"Aditi Dhir","orcid":"0000-0001-9974-0073","position":15,"is_corresponding":false},{"id":1427138,"name":"Kurt Statz-Geary","orcid":null,"position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:52:30.048313Z","pmid":"40563612","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":[]}