{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T20:11:26Z","timestamp":1776543086740,"version":"3.51.2"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Ewing Sarcoma (EWS) has been reported in seven children with Down syndrome (DS). To date, a detailed assessment of this solid tumour in DS patients is yet to be made.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we characterise a chemo-resistant mediastinal EWS in a 2-year-old DS child, the youngest ever reported case, by exploiting sequencing approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The tumour showed a neuroectodermal development driven by the EWSR1-FLI1 fusion. The inherited myeloperoxidase deficiency of the patient caused failure of neutrophil-mediated cell death and promoted genomic instability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In this context, the tumour underwent genome-wide near haploidisation resulting in a massive overexpression of pro-inflammatory cytokines. Recruitment of defective neutrophils fostered rapid evolution of this EWS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2024.1429833","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T05:10:37Z","timestamp":1727932237000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Impaired neutrophil-mediated cell death drives Ewing\u2019s Sarcoma in the background of Down syndrome"],"prefix":"10.3389","volume":"14","author":[{"given":"Serena","family":"Peirone","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Tirtei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Campello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Parlato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simonetta","family":"Guarrera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Mareschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Marini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian Dorin","family":"Asaftei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Bertero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Papotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Priante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Cereda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franca","family":"Fagioli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1706537","article-title":"Down syndrome","volume":"382","author":"Bull","year":"2020","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"655","DOI":"10.3390\/brainsci11050655","article-title":"Is the age of developmental milestones a predictor for future development in down syndrome","volume":"11","author":"Locatelli","year":"2021","journal-title":"Brain Sci"},{"key":"B3","first-page":"82","article-title":"Down syndrome from Epidemiologic Point of View","author":"Al-Biltagi","year":"2015","journal-title":"EC Paediatrics"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.164","article-title":"The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome","volume":"30","author":"Lee","year":"2016","journal-title":"Leukemia"},{"key":"B5","article-title":"A lack of neuroblastoma in Down syndrome: a study from 11 European countries","volume":"58","author":"Satg\u00e9","year":"1998","journal-title":"Cancer Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-012-1041-y","article-title":"A very rare cancer in Down syndrome: medulloblastoma. 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