GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327331/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327331GEOGSEfalseFrequency and prognostic significance of genetic abnormalities in a subgroup of intermediate risk neuroblastoma patients: A SIOPEN studyPURPOSE: Intermediate-risk neuroblastoma patients >18 months of age, with non-MYCN amplified, International Neuroblastoma Risk Group Staging System (INRGSS) localised, unresectable or International Neuroblastoma Staging System (INSS) stage 3 tumors, and unfavourable histology have inferior outcomes compared to other intermediate-risk patients. This study aimed to identify genetic prognostic biomarkers within this rare subgroup. PATIENTS AND METHODS: We conducted a large, international study including chromosomal copy number in all cases, next-generation DNA sequencing in most, and telomere maintenance mechanisms (TMM) and gene expression in a subset, and correlated results with patient survival. RESULTS: Among 98 tumors, 9/98 (9.2%) had oncogene amplifications (CDK4/MDM2/TERT co-amplification (n=1), CDK4/MDM2 co-amplification (n=4), CDK4 (n=2), TERT (n=1), and MYC (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%] (p<0.0001 log rank test) and 5-year overall survival (OS) [44.4% (95% CI: 21.4-92.3%)] (p <0.01 log rank test). Patients with tumors harbouring tSCAs had inferior EFS compared to those with numerical chromosomal aberrations only [51.7% (95% CI: 40.6-65.8%) vs. 93.3% (95% CI: 81.5-100%)] (p <0.01). Patients with p53 pathway tumor alterations (n=10) had worse EFS than those without [0% vs. 61.1% (95% CI: 50.3-74.3%)] (p <0.0001, log-rank test) and worse OS [26.7% (95% CI: 8.9-80.3%) vs. 80.9% (95% CI: 71.8-91.3%)] (p<0.001 log rank test). Multi-variable 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. CONCLUSION: 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.2026/07/15GSE327331GSM9653712GSM9653713GSM9653702GSM9653714GSM9653703GSM9653715GSM9653704GSM9653710GSM9653711GSM9653709GSM9653716GSM9653705GSM9653717GSM9653706GSM9653718GSM9653707GSM9653719GSM965370818573327331Homo sapiens[42385103]