NEURONAL SRC AND TRK A PROTOONCOGENE EXPRESSION IN NEUROBLASTOMAS ANDPATIENT PROGNOSIS

Neuroblastomas present a wide variety of clinical and biological behav iors, which are reflected by the heterogeneous expressions of protoonc ogenes related to the neuronal differentiation and amplification of th e N-myc gene. High expression of trk A and Ha-ras in neuroblastomas ha s been shown to be associated with an excellent patient outcome. We ha ve previously reported that neuron-specific src mRNA was increased in chemically differentiated neuroblastoma cell lines and in clinically o bserved neuroblastomas without N-myc amplification, In the present stu dy, to clarify both the value of neuronal c-srcN2 expression as a prog nostic indicator and the significance of the coexpression of these pho tooncogenes, we examined the expression of 3 alternatively spliced src , trk A and Ha-res in neuroblastoma tissues from 60 patients by compet itive RNA-polymerase chain reaction (PCR). The restates indicate that protooncogene expression in neuroblastomas correlated with a favorable outcome for c-srcN2 and trk A. N-myc gene was amplified exclusively i n tumors with low levels of trk A. Low expression of c-srcN2 and trk A might thus characterize different aggressive phenotypes due to differ ent signal transduction pathways of neural differentiation in neurobla stoma. The combined analyses for c-srcN2 and trk A expression by RNA-B CR should provide information about the biological phenotype of a neur oblastoma within a short period of time after obtaining tumor material . (C) 1998 Wiley-Liss, Inc.