{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T10:52:05Z","timestamp":1781520725671,"version":"3.54.1"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Japan Agency for Medical Research and Development (AMED) P-DIRECT","award":["JP15cm0106058"],"award-info":[{"award-number":["JP15cm0106058"]}]},{"name":"the Ministry of Health, Labor and Welfare of Japan for the Third Term Comprehensive 10-year Strategy for Cancer Control","award":["H19-010"],"award-info":[{"award-number":["H19-010"]}]},{"name":"the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI)","award":["20219782; 17874238; 26461603; 23591562; 24249061"],"award-info":[{"award-number":["20219782; 17874238; 26461603; 23591562; 24249061"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Neuroblastomas (NBs) exhibit broad and divergent clinical behaviors and tumor risk classification at diagnosis is crucial for the selection of an appropriate therapeutic strategy for each patient. The present study aimed to validate the clinical relevance of International Neuroblastoma Risk Group (INRG) prognostic and genomic markers in a Japanese NB cohort using a retrospective analysis. Follow-up data based on 30 common INRG queries in 605 NB cases diagnosed in Japan between 1990 and 2014 were collected and the genome signature of each tumor sample was integrated. As previously indicated, age, tumor stage, MYCN, DNA ploidy, the adrenals as the primary tumor site, serum ferritin and lactate dehydrogenase (LDH) levels, segmental chromosome aberrations, and the number of chromosome breakpoints (BP) correlated with lower survival rates, while the thorax as the primary tumor site and numerical chromosome aberrations correlated with a favorable prognosis. In the patient group with stage 4, MYCN non-amplified tumors (n = 225), one of the challenging subsets for risk stratification, age \u2265 18 months, LDH \u2265 1400 U\/L, and BP \u2265 7 correlated with lower overall and event-free survival rates (p &lt; 0.05). The genome subgroup GG-P2s (partial chromosome gain\/loss type with 1p\/11q losses and 17q gain, n = 30) was strongly associated with a lower overall survival rate (5-year survival rate: 34%, p &lt; 0.05). Therefore, the combination of the tumor genomic pattern (GG-P2s and BP \u2265 7) with age at diagnosis and LDH will be a promising predictor for MYCN-non-amplified high-risk NBs in patient subsets, in accordance with previous findings from the INRG project.<\/jats:p>","DOI":"10.3390\/biom12010018","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T10:16:18Z","timestamp":1640254578000},"page":"18","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Retrospective Analysis of INRG Clinical and Genomic Factors for 605 Neuroblastomas in Japan: A Report from the Japan Children\u2019s Cancer Group Neuroblastoma Committee (JCCG-JNBSG)"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9105-1142","authenticated-orcid":false,"given":"Miki","family":"Ohira","sequence":"first","affiliation":[{"name":"Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Takimoto","sequence":"additional","affiliation":[{"name":"Department of Childhood Cancer Data Management, National Center for Child Health and Development, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Saitama Children\u2019s Medical Center, Saitama 330-8777, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2515-1054","authenticated-orcid":false,"given":"Tomoro","family":"Hishiki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimikazu","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Children\u2019s Cancer Center, National Center for Child Health and Development, Tokyo 157-8535, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Shichino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Center for Global Health and Medicine, Tokyo 162-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1740-7096","authenticated-orcid":false,"given":"Tomoko","family":"Iehara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Nagase","sequence":"additional","affiliation":[{"name":"Division of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Fukushima","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Saitama Medical University International Medical Center, Saitama 350-1298, Japan"},{"name":"Department of Health Services Research, Institutes of Medicine, University of Tsukuba, Ibaraki 305-8576, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Division of Surgery, Surgical Oncology, National Center for Child Health and Development, Tokyo 157-8535, Japan"},{"name":"Division of Pediatric Surgical Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Tajiri","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Nakagawara","sequence":"additional","affiliation":[{"name":"Kyushu International Heavy Particle Beam Cancer Radiotherapy Center (SAGA HIMAT Foundation), Saga 841-0071, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4798-7546","authenticated-orcid":false,"given":"Takehiko","family":"Kamijo","sequence":"additional","affiliation":[{"name":"Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrc1014","article-title":"Neuroblastoma: Biological insights into a clinical enigma","volume":"3","author":"Brodeur","year":"2003","journal-title":"Nat. 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