PHYSICAL MAPPING OF THE DDX1 GENE TO 340 KB 5' OF MYCN

One of the most important prognostic factors in neuroblastoma is ampli fication of the MYCN gene, which is strongly associated with advanced stages of disease and a poor prognosis. Although the MYCN amplicon som etimes spans more than 1 Mb, no other consistently expressed sequences from the MYCN amplicon have been reported. However, DDX1, a gene enco ding a DEAD box protein, was recently mapped to chromosome 2p24 and is frequently co-amplified with MYCN. Therefore, we performed genomic ma pping with YACs to determine the physical relationship between DDX1 an d MYCN, and whether DDX1 was contained within the core region of ampli fication, Based on YAC restriction mapping and content analysis, DDX1 maps 340 kb 5' of MYCN, outside the core domain of consistent amplific ation. Interestingly, we also determined by sequence analysis and deta iled restriction mapping that G21, previously isolated as a 'neuroblas toma-specific' cDNA clone from an MYCN amplicon, is a partial cDNA of DDX1. Our data confirm that DDX1 is amplified in some but not all MYCN -amplified tumors, and that it is rearranged in other cases. This sugg ests that the co-amplification of DDX1 is due to its proximity to MYCN .