Neuroblastoma is a heterogeneous tumor that displays several numerical and structural copy number variations. Metastatic tumors of high-risk patients frequently show loss of chromosomes 1p, 4p, 9p, 11q and 14q, and gains of chromosomes 2p, 12p and 17q. Moreover, tumor tissue gene expression profiling is often abnormal in these patients. Many genes involved in cell cycle control are located in the damaged chromosome regions and/or are deregulated in their gene expression, suggesting that neuroblastoma onset and development greatly depends on the loss of cell cycle control. Recent studies have demonstrated that suppression of cyclin D1 expression or its kinase partner Cdk4 in neuroblastoma cells can restore the G1 checkpoint while high expression levels of Cdk2 is essential for the survival of neuroblastoma cells with MYCN amplification. Other cell cycle regulatory candidate genes such as BARD1, CHEK2 and PTPN11 have been found to be involved in the pathogenesis of neuroblastoma by genome-wide association studies and next-generation sequencing technologies. Integrative analysis of genome and transcriptome data from neuroblastoma samples has also identified genes active in the spindle formation at mitotic metaphase including AURKA and MAD2L1, which are important targets for therapy in neuroblastoma. The present chapter gives an overview of recent advances in the relationship between cell cycle genes and neuroblastoma.
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health