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Updated: Dec 31, 2025

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Genetic predisposition and chromosome instability in neuroblastoma
Gian Paolo Tonini1, Mario Capasso2,3
1Neuroblastoma Laboratory, Pediatric Research Institute, Città della Speranza, Corso Stati Uniti 4, 35127, Padova, Italy. gp.tonini@irpcds.org.
Abstract:
Neuroblastoma (NB) is a pediatric tumor of embryonic origin. About 1-2% of all NBs are familial cases, and genetic predisposition is suspected for the remaining cases. During the last decade, genome-wide association studies (GWAS) and high-throughput sequencing approaches have been used to identify associations among common and rare genetic variants and NB risk. Substantial data has been produced by large patient cohorts that implicate various genes in NB tumorigenesis, such as CASC15, BARD1, CHEK2, LMO1, LIN28B, AXIN2, BRCA1, TP53, SMARCA4, and CDK1NB. NB, as well as other pediatric cancers, has few recurrent mutations but several copy number variations (CNVs). Almost all NBs show both numerical and structural CNVs. The proportion between numerical and structural CNVs differs between localized and metastatic tumors, with a greater prevalence of structural CNVs in metastatic NB. This genomic chaos frequently identified in NBs suggests that chromosome instability (CIN) could be one of the major actors in NB oncogenesis. Interestingly, many NB-predisposing variants occur in genes involved in the control of genome stability, mitosis, and normal chromosome separation. Here, we discuss the relationship between genetic predisposition and CIN in NB.
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