Neuroblastoma is a pediatric tumor of the developing sympathetic nervous system that shows a broad spectrum of clinical and biological behaviour ranging from life-threatening progression to spontaneous regression and differentiation. Although substantial progress has been made in patients risk stratification over the last years, prediction of individual clinical courses still remains challenging. Many attempts have thus been made in the past to discriminate the diverse phenotypes of neuroblastoma at the transcriptome level using various technologies such as microarrays, SAGE and real-time PCR, however, none of these studies were able to comprehensively address this issue.

To precisely define prognostic gene signatures for each neuroblastoma subtype, we therefore have developed a neuroblastoma-specific oligonucleotide-microarray comprising probes for about 10 000 genes that have been selected on the basis of previous studies. This neuroblastoma array is currently evaluated by examination of approximately 150 pretreatment primary neuroblastoma samples in a retrospective study.

In this project, the array will be validated as part of the German Cooperative Neuroblastoma Trial NB 2004, which will enable us to analyze about 300 neuroblastoma specimens of newly diagnosed cases within three years. The study is expected to result in a refined classification of neuroblastoma subtypes and subsequently in improved clinical risk stratification. In addition, candidate genes showing strong association with particular biological subtypes of neuroblastoma will be functionally characterized in cooperation with other groups of the neuroblastoma network. The combined efforts of candidate genes will uncover molecular pathways that are fundamentally involved in the pathogenesis of the various subtypes of neuroblastoma and may thereby contribute to elucidate the general mechanisms of tumor progression and spontaneous regression.