A functional gene map is required to adapt therapy of metastatic neuroblastoma

Neuroblastoma is a very common solid tumor which arises in childhood and sh ows an extreme heterogeneity at the clinical, histological and genetic leve ls. Besides age and stage, N-myc amplification and 1p deletion are prognost ic factors of the disease: in Europe, these genetic markers are used to con duct therapy. In France, N-myc amplification is a factor of bad prognosis w hich lead; in all forms of the disease including localised forms and metast atic forms of children aged of less than 1 year, to a myeloablative treatme nt with autologous hematopoietic stem cells transplantation. By contrast N- myc amplification has no impact on the survival of children aged of more th an 1 year with a poor prognosis (30% overall survival, 5 years) but, this g enetic abnormality is taken into account to treat primary tumor of these pa tients. In an attempt to find out prognostic factors of these aggressive fo rms oft-he disease, various pathways (apoptosis, differentiation angiogenes is, detoxication, immune response) have been recently surveyed, but studies have been carried out on a limited number of genes. Moreover, experimental models of human metastatic neuroblastoma have been obtained in which varia tions of genes transcript levels involved in these pathways, are observed. The current break-through of cDNA microarrays allows to develop a dynamic t ranscriptomic scanning of these models as well as of tumors and bone marrow s from patients upon conventional chemotherapy. This technology will enable : i) to define molecular entities of the metastatic disease; ii) to apply a dapted treatment; iii) to develop new therapeutic strategies.