{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T13:13:33Z","timestamp":1784207613145,"version":"3.55.0"},"reference-count":48,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>\n                      Intermediate-risk neuroblastoma patients older than 18 months, with non\u2013\n                      <jats:italic toggle=\"yes\">MYCN<\/jats:italic>\n                      amplified, International Neuroblastoma Risk Group Staging System localized, unresectable or International Neuroblastoma Staging System stage 3 tumors, and unfavorable histology have inferior outcomes compared with other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms and gene expression in a subset, and correlated results with patient survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Among 98 tumors, 9\/98 (9.2%) had oncogene amplifications (\n                      <jats:italic toggle=\"yes\">CDK4\/MDM2\/TERT<\/jats:italic>\n                      coamplification (n = 1),\n                      <jats:italic toggle=\"yes\">CDK4\/MDM2<\/jats:italic>\n                      coamplification (n = 4),\n                      <jats:italic toggle=\"yes\">CDK4<\/jats:italic>\n                      (n = 2),\n                      <jats:italic toggle=\"yes\">TERT<\/jats:italic>\n                      (n = 1), and\n                      <jats:italic toggle=\"yes\">MYC<\/jats:italic>\n                      (n = 1)), while 63\/98 (64.3%) had typical segmental chromosomal aberrations (tSCAs). Patients with tumors with oncogene amplification had the worst 5-year event-free survival (EFS; 0%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001 log-rank test) and 5-year overall survival (OS; 44.4% [95% CI, 21.4 to 92.3];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .01 log-rank test). Patients with tumors harboring tSCAs had inferior EFS compared with those with numerical chromosomal aberrations only (51.7% [95% CI, 40.6 to 65.8]\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      93.3% [95% CI, 81.5 to 100];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .01). Patients with p53 pathway tumor alterations (n = 10) had worse EFS than those without (0%\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      61.1% [95% CI, 50.3 to 74.3];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .0001, log-rank test) and worse OS (26.7% [95% CI, 8.9 to 80.3]\n                      <jats:italic toggle=\"yes\">v<\/jats:italic>\n                      80.9% [95% CI, 71.8 to 91.3];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001 log-rank test). Multivariable analysis identified tSCAs as an independent prognostic variable for EFS and oncogene amplification or p53 pathway abnormalities as independent prognostic variables for EFS and OS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Oncogene amplification and\/or p53 pathway abnormalities and\/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-26-00045","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T19:59:11Z","timestamp":1782935951000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Frequency and Prognostic Significance of Genetic Abnormalities in a Subgroup of Patients With Intermediate-Risk Neuroblastoma: A SIOPEN Study"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3613-0845","authenticated-orcid":true,"given":"Hannah E.","family":"Hartley","sequence":"first","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom"},{"name":"Children's Cancer Institute, Health Translational Hub, Randwick, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7771-3840","authenticated-orcid":true,"given":"Fang Chyi","family":"Fong","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom"},{"name":"Research Department, National Cancer Council (MAKNA), Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alem S.","family":"Gabriel","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise K.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6484-4623","authenticated-orcid":true,"given":"Emily","family":"Beckett","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8957-6609","authenticated-orcid":true,"given":"Lisa M.","family":"Allinson","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3010-5757","authenticated-orcid":true,"given":"Angharad","family":"Goodman","sequence":"additional","affiliation":[{"name":"Newcastle Genetics Laboratory, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Potts","sequence":"additional","affiliation":[{"name":"Newcastle Genetics Laboratory, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Whittle","sequence":"additional","affiliation":[{"name":"Newcastle Genetics Laboratory, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruby","family":"Barford","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5867-6072","authenticated-orcid":true,"given":"Alice","family":"Lamparelli","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Herd","sequence":"additional","affiliation":[{"name":"Department of Paediatric Oncology, Royal Aberdeen Children's Hospital, Aberdeen, Scotland, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6599-5681","authenticated-orcid":true,"given":"Katia","family":"Mazzocco","sequence":"additional","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6321-5701","authenticated-orcid":false,"given":"Annalisa","family":"Pezzolo","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2569-4515","authenticated-orcid":true,"given":"Martina","family":"Morini","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6008-9356","authenticated-orcid":true,"given":"Martina","family":"Ardito","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Eva","sequence":"additional","affiliation":[{"name":"Scientific Directorate, IRCCS Istituto Giannina Gaslini, Genova, 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