EXPRESSION OF NEURONAL SRC MESSENGER-RNA AS A FAVORABLE MARKER AND INVERSE CORRELATION TO N-MYC GENE AMPLIFICATION IN HUMAN NEUROBLASTOMAS

Neuron-specific src mRNA, which is expressed in human brain tissue by alternative splicing, is associated with neural differentiation. Neuro nal c-srcNI expression may be associated with the ability of neuroblas tomas to mature; furthermore, c-srcN2 mRNA is induced in chemically di fferentiated neuroblastoma cells in vitro. The prognosis of a patient with a neuroblastoma is strongly affected by the ability of the tumor to differentiate in vivo. In order to clarify the relationship between neuronal src mRNA expression and the clinical outcome of a neuroblast oma, we analyzed the expression of src mRNA in neuroblastoma tissues f rom 28 patients by SI-nuclease-protection assay. N-myc gene amplificat ion was also examined by Southern blot hybridization. The clinical sig nificance of neuronal src mRNA expression and its relevance to N-myc g ene amplification was also investigated. A high ratio (more than 10%) of c-srcN2 mRNA expression was observed in all early-stage tumors and in advanced neuroblastomas with a favorable prognosis. In contrast, in advanced neuroblastomas with an aggressive clinical phenotype, c-srcN 2 mRNA expression ws found at a low ratio (below 10%). Genome amplific ation of the N-myc gene and expression of c-srcN2 mRNAs were inversely correlated. When combined with other prognostic markers such as N-myc gene amplification, the expression of c-srcN2 mRNA may be a new biolo gical marker to predict the prognosis of patients with neuroblastomas.