The DDX1 Gene Maps Within 400 Kbp 5' to MYCN and is Frequently Coamplified in Human Neuroblastoma

Human neuroblastoma cells frequently show amplification of the oncogene MYCN, which maps to 2p24. Previous studies have localized the DEAD box motif gene DDX1 to the same chromosome band and demonstrated coamplification of DDX1 and MYCN in two retinoblastoma cell lines. Recently, a high frequency of coamplification of DDX1 and MYCN has been shown in human neuroblastoma cells. We have determined the physical distance between the two genes by pulsed field gel electrophoresis in normal tissue and have found that DDX1 maps to a position at a maximum distance of 400 kbp 5' to MYCN. Two neuroblastoma cell lines with coamplification of DDX1/MYCN showed a similar topographic relationship of the two genes. In contrast, in two cell lines with high copy number, the DDX1 gene was not present in all amplified units recognized by MYCN and had changed its position in the amplified DNA relative to MYCN from 5' to 3', presumably by rearrangement during the amplification process. Our data show that the high frequency of DDX1 coamplification is due to its close physical distance to MYCN. Although amplification has resulted in an elevated expression of DDX1 the significance of overexpression for neuroblastoma remains unclear.