TRANSCRIPTIONAL ACTIVITY OF N-MYC AND NGF-R IN 50 PRIMARY HUMAN NEUROBLASTOMAS AS PREDICTOR FOR CLINICAL OUTCOME

Abstract

N-myc oncogene amplification in human neuroblastoma predicts an unfavourable prognosis for the patients. Even for patients with a single copy of N-myc the survival probability is only about 70%. To specify the prognosis of patients with N-myc non-amplified neuroblastoma we performed RNA expression analyses of genes related to neural differentiation in 50 primary neuroblastomas, i.e. examined the proto-oncogene N-myc and ngf-r, the gene for the nerve growth factor receptor (NGF-r), in the same tumor tissue. We found that patients with high levels of ngf-r expression, seen in 67% of stage I, II and IVs and in 59% of stage III and IV tumors, had a probability of survival of 100% in the presence of no or low levels of N-myc expression and a non-amplified N-myc in all cases. Low ngf-r expression levels were seen in 31% of stage III and IV tumors in comparison to only 5% in stage I, II, and IVs, accompanied by low, medium or high N-myc transcriptional activity and a non-amplified N-myc in 30%, and this indicates a probability of survival of only approximately 50%. Tumors characterized by medium expression levels of ngf-r and N-myc have a probability of survival of about 80%. In conclusion, RNA expression measurements, as performed for ngf-r and N-myc, can delineate prognostic subgroups within defined clinical stages and N-myc non-amplified tumors and thus, be utilized as prognostic indicators in human neuroblastoma.