Rare Frequencey of Point Mutations For Codon 12, 13 and 61 of Ras Gene In Italian Neuroblastoma

Single point mutations of ras oncogenes are found in many tumors and contribute to the pathogenesis of the cancer. The product of the ras gene, p21 protein, was found expressed in several neuroblastoma tissues. However, the role of ras gene in this tumor has yet to be clarified. To contribute to the understanding of the ras activation, 79 fresh biopsies of neuroblastoma were studied to investigate the possibility that ras would be activated by point mutation. Analysis of H-ras and N-ras was performed by means of PCR and SSO, while K-ras mutations were detected by multiplex-ASPCR. None of the neuroblastomas examined showed H- or K-ras activation, while N-ras mutations were demonstrated in only three patients (3,7%). N-myc oncogene is amplified in a substantial number of patients with neuroblastoma. N-myc amplification was studied by Southern blot technique. N-myc amplification was demonstrated in 13.2% of patients less than 1 year of age at diagnosis and 23% of older children. Two of the patients (one stage I and one stage IVs) with N-ras mutation and without N-myc amplification had a good outcome, while the third (stage IVs) with N-myc amplification had a poor prognosis. These results suggest that ras activation is a rare event in both amplified and non-amplified neuroblastoma tumors and that N-ras activation was not involved in the clinical outcome of these patients. Moreover, our data suggest that p21 expression is induced by a post-transcriptional activation.