{"doi":"10.1093/neuonc/noab034","title":"Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q","abstract":"BACKGROUND: Within PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification. METHODS: Five independent non-overlapping cohorts of PF-EPN-A were analyzed applying genome-wide methylation arrays for chromosomal and clinical variables predictive of survival. RESULTS: Across all cohorts, 663 PF-EPN-A were identified. The most common broad copy number event was 1q gain (18.9%), followed by 6q loss (8.6%), 9p gain (6.5%), and 22q loss (6.8%). Within 1q gain tumors, there was significant enrichment for 6q loss (17.7%), 10q loss (16.9%), and 16q loss (15.3%). The 5-year progression-free survival (PFS) was strikingly worse in those patients with 6q loss, with a 5-year PFS of 50% (95% CI 45%-55%) for balanced tumors, compared with 32% (95% CI 24%-44%) for 1q gain only, 7.3% (95% CI 2.0%-27%) for 6q loss only and 0 for both 1q gain and 6q loss (P = 1.65 × 10-13). After accounting for treatment, 6q loss remained the most significant independent predictor of survival in PF-EPN-A but is not in PF-EPN-B. Distant relapses were more common in 1q gain irrespective of 6q loss. RNA sequencing comparing 6q loss to 6q balanced PF-EPN-A suggests that 6q loss forms a biologically distinct group. CONCLUSIONS: We have identified an ultra high-risk PF-EPN-A ependymoma subgroup, which can be reliably ascertained using cytogenetic markers in routine clinical use. A change in treatment paradigm is urgently needed for this particular subset of PF-EPN-A where novel therapies should be prioritized for upfront therapy.","journal":"Neuro-Oncology","year":2021,"id":151241,"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":84,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8989,"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":642771,"name":"Lakshmikirupa Sundaresan","orcid":"0000-0002-9534-7810","position":1,"is_corresponding":false},{"id":643761,"name":"Ayala Heled","orcid":null,"position":2,"is_corresponding":false},{"id":642772,"name":"Hallie Coltin","orcid":"0000-0003-0820-6276","position":3,"is_corresponding":false},{"id":25334,"name":"Kristian W. Pajtler","orcid":"0000-0002-3562-6121","position":4,"is_corresponding":false},{"id":226934,"name":"Tong Lin","orcid":"0000-0003-1181-3763","position":5,"is_corresponding":false},{"id":302803,"name":"Thomas E. Merchant","orcid":"0000-0002-0412-6255","position":6,"is_corresponding":false},{"id":70188,"name":"Roger E. McLendon","orcid":"0000-0001-6682-4588","position":7,"is_corresponding":false},{"id":240508,"name":"Cláudia C. Faria","orcid":"0000-0003-1259-9922","position":8,"is_corresponding":false},{"id":643762,"name":"Molly K. Buntine","orcid":null,"position":9,"is_corresponding":false},{"id":642773,"name":"Christine L. White","orcid":"0000-0002-5920-0029","position":10,"is_corresponding":false},{"id":5562,"name":"Stefan M. Pfister","orcid":"0000-0002-5447-5322","position":11,"is_corresponding":false},{"id":109755,"name":"Mark R. Gilbert","orcid":"0000-0003-2556-9722","position":12,"is_corresponding":false},{"id":292546,"name":"Terri S. Armstrong","orcid":"0000-0002-2414-0492","position":13,"is_corresponding":false},{"id":351812,"name":"Éric Bouffet","orcid":"0000-0002-6832-6539","position":14,"is_corresponding":false},{"id":240506,"name":"Sachin Kumar","orcid":"0000-0002-4853-3864","position":15,"is_corresponding":false},{"id":240514,"name":"Michael D. Taylor","orcid":"0000-0001-7009-3466","position":16,"is_corresponding":false},{"id":13200,"name":"Kenneth Aldape","orcid":"0000-0001-5119-7550","position":17,"is_corresponding":false},{"id":271073,"name":"David W. Ellison","orcid":"0000-0003-1239-7757","position":18,"is_corresponding":false},{"id":642774,"name":"Nicholas G. Gottardo","orcid":"0000-0002-1082-6776","position":19,"is_corresponding":false},{"id":13674,"name":"Marcel Kool","orcid":"0000-0002-6557-5468","position":20,"is_corresponding":false},{"id":13676,"name":"Andrey Korshunov","orcid":"0000-0002-5257-3623","position":21,"is_corresponding":false},{"id":246738,"name":"Jordan R. Hansford","orcid":"0000-0001-7733-383X","position":22,"is_corresponding":false},{"id":240488,"name":"Vijay Ramaswamy","orcid":"0000-0002-6557-895X","position":23,"is_corresponding":false},{"id":642770,"name":"Lorena Baroni","orcid":"0000-0002-1599-7080","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-18T23:43:11.293086Z","pmid":"33580238","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":[]}