Genetic predisposition and chromosome instability in neuroblastoma

  • Gian Paolo ToniniEmail author
  • Mario CapassoEmail author


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.


Neuroblastoma Chromosome instability Allelic variance Mutation SNP 



Chromosome instability


Genome-wide association studies


Next generation sequencing


Single nucleotide polymorphisms


Neural crest cells


Copy number variations


Hirschsprung disease


Congenital central hypoventilation syndrome


Long noncoding RNA


Microarray-comparative genomic hybridization


Funding information

The work has been supported by the Italian Neuroblastoma Foundation (to GPT and MC), Associazione Italiana per la Ricerca sul Cancro (Grant No. 19255 to M.C.), Regione Campania “SATIN” grant no. 2018–2020 (to M.C.). Fondazione Italiana per la Lotta al Neuroblastoma (to M.C.); Associazione Oncologia Pediatrica e Neuroblastoma (to M.C.)

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Neuroblastoma Laboratory, Pediatric Research InstituteCittà della SperanzaPadovaItaly
  2. 2.Dipartimento di Medicina Molecolare e Biotecnologie MedicheUniveristà degli Studi di Napoli Federico IINaplesItaly
  3. 3.CEINGE Biotecnologie AvanzateNaplesItaly

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