{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:51:49Z","timestamp":1787500309331,"version":"build-2736575974"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Science for Children"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Choroid plexus carcinomas (CPCs) are rare aggressive pediatric tumors of the brain with no treatment standards. Genetic profiling of CPCs is often confined to possible association with Li\u2013Fraumeni syndrome, though only about a half of CPCs develop from syndromic predispositions. Whole-chromosome gains and losses typical of CPCs reflect genomic instability of these tumors, but only partially explain the aggressive clinical course.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study enrolled 25 pediatric patients with CPC, receiving treatment between January 2009 and June 2022. Molecular-genetic testing was performed for 20 cases with available tumor tissue and encompassed mutational status, chromosomal aberrations, and gene expression profiles. We analyzed several factors presumably influencing the outcomes, including molecular profiles and clinical parameters. The median follow-up constituted 5.2 years (absolute range 2.8\u201312.6 years).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All studied CPCs had smooth mutational profiles with the only recurrent event being TP53 variants, either germline or somatic, encountered in 13 cases. Unbalanced whole-chromosome aberrations, &amp;#x2028;notably multiple monosomies, were highly typical. In 7 tumors, chromosome losses were combined with complex genomic rearrangements: segmental gains and losses or signs of chromothripsis. This phenomenon was associated with extremely low 5-year survival: 20.0 \u00b1 17.9% vs 85.7 \u00b1 13.2%; P = .009. Transcriptomically, the cohort split into 2 polar clusters Ped_CPC1 and Ped_CPC2 differing by survival: 31.3 \u00b1 17.8% vs 100%; P = .012.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CPCs split into at least 2 molecular subtypes distinguished both genomically and transcriptomically. Clusterization of the tumors into Ped_CPC1 and Ped_CPC2 significantly correlates with survival. The distinction may prove relevant in clinical trials for dedicated and patient-oriented optimization of clinical protocols for these rare tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noac274","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T20:27:16Z","timestamp":1671136036000},"page":"1132-1145","source":"Crossref","is-referenced-by-count":12,"title":["Molecular heterogeneity of pediatric choroid plexus carcinomas determines the distinctions in clinical course and prognosis"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2015-5790","authenticated-orcid":false,"given":"Margarita","family":"Zaytseva","sequence":"first","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2977-665X","authenticated-orcid":false,"given":"Andge","family":"Valiakhmetova","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3007-3772","authenticated-orcid":false,"given":"Ludmila","family":"Yasko","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Samarin","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila","family":"Papusha","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5461-7442","authenticated-orcid":false,"given":"Anastasia","family":"Shekhtman","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Usman","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill","family":"Voronin","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Karachunskiy","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2322-5734","authenticated-orcid":false,"given":"Galina","family":"Novichkova","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1308-8622","authenticated-orcid":false,"given":"Alexander","family":"Druy","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology , Moscow , Russia"},{"name":"Research Institute of Medical Cell Technologies , Yekaterinburg , Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"issue":"1","key":"2023060217132647200_CIT0001","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s11060-014-1616-x","article-title":"Choroid plexus tumor epidemiology and outcomes: implications for surgical and radiotherapeutic management","volume":"121","author":"Cannon","year":"2015","journal-title":"J Neurooncol."},{"key":"2023060217132647200_CIT0002","volume-title":"World Health Organization Classification of Tumours of the Central Nervous System","author":"WHO Classification of Tumours Editorial Board.","year":"2021","edition":"5"},{"issue":"12","key":"2023060217132647200_CIT0003","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1200\/JCO.2009.26.8169","article-title":"TP53 alterations determine clinical subgroups and survival of patients with choroid plexus tumors","volume":"28","author":"Tabori","year":"2010","journal-title":"J Clin Oncol."},{"issue":"3","key":"2023060217132647200_CIT0004","doi-asserted-by":"crossref","first-page":"e18015","DOI":"10.1371\/journal.pone.0018015","article-title":"Increased incidence of choroid plexus carcinoma due to the germline TP53 R337H mutation in southern Brazil","volume":"6","author":"Custodio","year":"2011","journal-title":"PLoS One."},{"issue":"6","key":"2023060217132647200_CIT0005","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1002\/pbc.23349","article-title":"Choroid plexus tumors; management, outcome, and association with the Li-Fraumeni syndrome: the Children\u2019s Hospital Los Angeles (CHLA) experience, 1991-2010","volume":"58","author":"Gozali","year":"2012","journal-title":"Pediatr Blood Cancer."},{"key":"2023060217132647200_CIT0006","doi-asserted-by":"crossref","first-page":"751784","DOI":"10.3389\/fonc.2021.751784","article-title":"Choroid plexus carcinomas with TP53 germline mutations: management and outcome","volume":"11","author":"Li","year":"2021","journal-title":"Front Oncol."},{"issue":"1","key":"2023060217132647200_CIT0007","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1158\/1078-0432.CCR-14-1324","article-title":"Molecular characterization of choroid plexus tumors reveals novel clinically relevant subgroups","volume":"21","author":"Merino","year":"2015","journal-title":"Clin Cancer Res."},{"issue":"4","key":"2023060217132647200_CIT0008","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1093\/neuonc\/noaa267","article-title":"The genetic landscape of choroid plexus tumors in children and adults","volume":"23","author":"Thomas","year":"2021","journal-title":"Neuro Oncol."},{"issue":"5","key":"2023060217132647200_CIT0009","doi-asserted-by":"crossref","first-page":"CS37","DOI":"10.12659\/MSM.882720","article-title":"A novel TP53 somatic mutation involved in the pathogenesis of pediatric choroid plexus carcinoma","volume":"18","author":"Lv","year":"2012","journal-title":"Med Sci Monit."},{"key":"2023060217132647200_CIT0010","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.wneu.2018.07.284","article-title":"Widely metastatic choroid plexus carcinoma associated with novel TP53 somatic mutation","volume":"119","author":"Baksh","year":"2018","journal-title":"World Neurosurg."},{"issue":"5","key":"2023060217132647200_CIT0011","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/gcc.22148","article-title":"Choroid plexus carcinomas are characterized by complex chromosomal alterations related to patient age and prognosis","volume":"53","author":"Ruland","year":"2014","journal-title":"Genes Chromosomes Cancer"},{"issue":"2","key":"2023060217132647200_CIT0012","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/NEN.0000000000000154","article-title":"High-resolution genomic analysis does not qualify atypical plexus papilloma as a separate entity among choroid plexus tumors","volume":"74","author":"Japp","year":"2015","journal-title":"J Neuropathol Exp Neurol."},{"issue":"6","key":"2023060217132647200_CIT0013","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1093\/neuonc\/nov322","article-title":"Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups","volume":"18","author":"Thomas","year":"2016","journal-title":"Neuro Oncol."},{"issue":"5","key":"2023060217132647200_CIT0014","doi-asserted-by":"crossref","first-page":"398","DOI":"10.3171\/2012.8.PEDS12132","article-title":"Treatment of choroid plexus tumors: a 20-year single institutional experience","volume":"10","author":"Bettegowda","year":"2012","journal-title":"J Neurosurg Pediatr"},{"key":"2023060217132647200_CIT0015","doi-asserted-by":"crossref","first-page":"106454","DOI":"10.1016\/j.clineuro.2020.106454","article-title":"Management of choroid plexus tumours: a comprehensive study from a tertiary hospital","volume":"201","author":"Konar","year":"2021","journal-title":"Clin Neurol Neurosurg."},{"issue":"1","key":"2023060217132647200_CIT0016","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s11060-017-2561-2","article-title":"A French retrospective study on clinical outcome in 102 choroid plexus tumors in children","volume":"135","author":"Siegfried","year":"2017","journal-title":"J Neurooncol."},{"key":"2023060217132647200_CIT0017","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1016\/j.wneu.2021.04.049","article-title":"Intracranial choroid plexus carcinomas: report of 11 cases from a single 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carcinoma","volume":"116","author":"Sun","year":"2014","journal-title":"J Neurooncol."},{"issue":"5","key":"2023060217132647200_CIT0025","doi-asserted-by":"crossref","first-page":"e29486","DOI":"10.1002\/pbc.29486","article-title":"Long-term survival of a patient with metastatic choroid plexus carcinoma, de novo germline TP53 mutated, after craniospinal proton irradiation","volume":"69","author":"Valiakhmetova","year":"2022","journal-title":"Pediatr Blood Cancer."},{"issue":"1","key":"2023060217132647200_CIT0026","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13148-019-0708-z","article-title":"DNA methylation signature is prognostic of choroid plexus tumor aggressiveness","volume":"11","author":"Pienkowska","year":"2019","journal-title":"Clin Epigenetics."},{"key":"2023060217132647200_CIT0027","doi-asserted-by":"crossref","first-page":"652","DOI":"10.3389\/fphar.2017.00652","article-title":"Molecular guided therapy provides sustained clinical response in refractory 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