Neuroblastoma: Role of MDM2 and SNP309 as Markers

MDM2 is a major negative regulator of p53 and in some tumors that present a wild type p53 gene deregulated expression of MDM2 could contribute to tumor development. In particular, in neuroblastoma, an extracranial pediatric tumor with unfrequent genetic inactivation of p53, deregulation of MDM2 could significantly decrease the activity of p53, resulting in failure of p53-regulated functions such as cell cycle arrest, apoptosis and sene­scence. A single nucleotide polymorphism (SNP309,T>G change; rs 2279744) in the MDM2 promoter increases the affinity for the transcription factor SP1, enhancing MDM2 expression and attenuating the activity of the p53 pathway. In this chapter, we review the role of MDM2 and its SNP309 on neuroblastoma development and progression and discuss future pharmacological approaches based on the presence of this polymorphism.