Neuroblastoma: Role of Clusterin as a Tumor Suppressor Gene

Abstract

Neuroblastoma is a paediatric malignancy originating from the peripheric nervous system, with an incidence of ∼11 cases per million children in Europe. In spite of the relatively low number of patients diagnosed with neuroblastoma every year, this disease accounts for a large portion of cancer mortality in infants, indicating that it has a very significant clinical impact. Intelligently designed compounds, developed on the basis of a growing understanding of the molecular networks deregulated in common types of adult and paediatric cancers, are leading to a better outcome of neoplastic diseases. However, we still need to elucidate the key molecular networks activated or inactivated in neuroblastoma, in order to tailor clinical interventions that are more specific and less toxic to children. Despite aggressive, multi modal chemotherapeutic drug treatments, metastatic neuroblastoma is still largely incurable and survivors have to endure the long-term consequences of drug toxicity. One of the critical determinants of neuroblastoma aggressiveness is the MYCN protooncogene, which is amplified in ∼25% of neuroblastomas. MYCN is a transcription factor that binds to the regulatory region of target genes, inducing their activation or inactivation. In our laboratory, we have recently identified Clusterin, also known as CLU, ApoJ or Apolipoprotein J, as a significant MYCN target gene in neuroblastoma. In this chapter we will discuss the biology of Clusterin, its role as a neuroblastoma suppressor gene and the potential clinical implications.