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  • Title: Co-amplification of MYCN and a DEAD box gene (DDX1) in primary neuroblastoma.
    Author: Squire JA, Thorner PS, Weitzman S, Maggi JD, Dirks P, Doyle J, Hale M, Godbout R.
    Journal: Oncogene; 1995 Apr 06; 10(7):1417-22. PubMed ID: 7731693.
    Abstract:
    DEAD box proteins are putative RNA helicases that have been implicated in cellular processes involving alteration of RNA secondary structure, such as translation initiation and splicing. These proteins share eight conserved amino acid motifs, including Asp(D)-Glu-(E)-Ala(A)-Asp(D) which is part of a more extended motif. Recently, we have shown that the novel DDX1 gene containing a DEAD box motif maps to the same chromosome band as MYCN at 2p24 and is co-amplified with MYCN in retinoblastoma cell lines. Here, we show that the DDX1 gene is co-amplified with the MYCN gene in 2 of three neuroblastoma cell lines and that DDX1 RNA levels correlate with DDX1 gene copy number. Since amplification of MYCN is an indicator of poor prognosis in neuroblastoma, it was of interest to determine whether co-amplification with DDX1 occurred in clinical samples of neuroblastoma and whether such a finding carried any additional prognostic significance. We determined the gene copy number of DDX1 in 32 neuroblastoma patient samples (representative of all stages): 13 were MYCN amplified and 19 had normal copy numbers of the MYCN gene. Of the 13 neuroblastomas that were MYCN amplified, seven were also DDX1 amplified. Of the 19 that were not MYCN amplified, none were DDX1 amplified. This is the first example of a gene that is co-amplified with MYCN at a high frequency in neuroblastoma. While there was a trend towards a worse clinical outcome with co-amplification, the numbers were too small to reach significance.
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