Pediatric Neuroblastoma: Molecular Detection of Minimal Residual Disease

Abstract

Real-time quantitative (RQ)-PCR for detection of minimal residual disease (MRD) in children with neuroblastoma can be used for evaluation of the presence of neuroblastoma in the bone morrow (BM) at diagnosis and during treatment. On the one hand, adding MRD testing by RQ-PCR to conventional BM testing at diagnosis might detect patients in the non-high risk group with BM invasion, thereby identifying patients that might benefit from more intensive treatment. On the other hand, a major goal of clinical MRD studies is to use MRD to measure response to therapy in high risk patients, to distinguish those high risk patients that will be cured by current therapies from those that need new or other therapies. In this way, PCR guided therapy might eventually result in better survival rates. Furthermore, when PCR assays are standardized internationally, response to different treatment schedules, including new therapies can be accurately compared. The most commonly used and most widely evaluated marker for molecular MRD detection in neuroblastoma is the rate limiting enzyme in the catecholamine synthesis, tyrosine hydroxylase (TH). Standard operating procedures (SOPs) have been recommended for TH mRNA detection by International Neuroblastoma Risk Group (INRG) Task Force to achieve international consensus. Recently, PHOX2B, a more sensitive and specific marker than TH has been described. This marker is currently evaluated alongside TH in prospective studies. The use of multiple markers next to TH and PHOX2B might also improve the sensitivity and the specificity of neuroblastoma detection. In this chapter the methodology of MRD detection by RQ-PCR and the clinical value of molecular detection in neuroblastoma patients is discussed.