Genetic predisposition and chromosome instability in neuroblastoma

AbstractNeuroblastoma (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. S ubstantial data has been produced by large patient cohorts that implicate various genes in NB tumorigenesis, such asCASC15,BARD1,CHEK2,LMO1,LIN28B,AXIN2, BRCA1, TP53,SMARCA4, andCDK1NB. 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.
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research

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