In vivo elimination of acentric double minutes containing amplified MYCN from neuroblastoma tumor cells through the formation of micronuclei

Neuroblastoma, the most common solid extracranial neoplasm in children, sho ws an appreciable variability in clinical evolution. Amplification of the M YCN oncogene in this tumor is detected in 25 to 30% of cases and is associa ted with poor clinical outcome. in this study, quantitative polymerase chai n reaction and fluorescence in situ hybridization were used to determine MY CN amplification status in 46 neuroblastoma tumors. MYCN amplification was detected in tumors from 11 patients. Fluorescence in situ hybridization rev ealed the presence of micronuclei containing amplified MYCN sequences in 8 of the 11 tumors. Micronuclei are indicative of spontaneous elimination or loss of amplified sequences by tumor cells. Because the elimination of ampl ified sequences can be enhanced in vitro by specific drugs such as hydroxyu rea, our observations suggest a new therapeutic strategy specifically targe ted to cells with amplified genes.