1653

DDX1

DBP-RB|UKVH5d;DEAD (Asp-Glu-Ala-Asp) box polypeptide 1;DDX1;DEAD (Asp-Glu-Ala-Asp) box polypeptide 1

ATP-dependent RNA helicase DDX1|DEAD box polypeptide 1|DEAD box protein 1|DEAD box protein retinoblastoma|DEAD box-1|DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 1

2p24

protein-coding

Combined analysis of gene expression array data and array-based comparative genomic hybridization data have been used in a series of 26 pediatric brain tumors to define up- and downregulated genes that coincide with losses, gains, and amplifications involving specific chromosome regions. Frequent losses were defined in chromosome arms 3q, 6q, 8p, 10q, 16q, 17p, and gains were identified in chromosome 7, and chromosome arms 9p and 17q. Amplification of a 2p region was seen in only one tumor, which corresponded to increased expression of the MYCN and DDX1 genes. To facilitate the analysis of the two data sets, we have developed a custom overlay tool that defines genes that are underexpressed in regions of deletions and overexpressed in regions of gain, across the genome andspecifically within regions showing recurrent involvement in medulloblastomas.#CI- Copyright 2006 Wiley-Liss, Inc.

Analysis of hereditary and nonhereditary retinoblastoma led to the formulation of the two-hit hypothesis of cancer in the early 1970s. The two-hit hypothesis was validated in the 1980s when both copies of the RB1 gene were shown to be mutatedin hereditary and nonhereditary retinoblastoma. However, consistent genetic abnormalities other than RB1 mutations suggest that additional events may be required for the formation of these malignant tumors. For example, MYCN amplification has long been known to occur in both retinoblastoma and neuroblastoma tumors and is strongly associated with poor prognosis in neuroblastoma. The DEAD box gene, DEAD box 1 (DDX1), is often coamplified with MYCN in both these childhood tumors. Here, we examine possible roles for DDX1 overexpression in retinoblastoma and neuroblastoma.

Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer that is related to the skeletal muscle lineage and characterized by recurrent chromosomal translocations. Within the ARMS category, there is clinical and genetic heterogeneity, consistent with the premise that "primary" genetic events collaborate with "secondary" events to give rise to subsets with varying clinical features. Previous studies demonstrated that genomic amplification occurs frequently in ARMS. In the current study, we used oligonucleotide arrays to localize two common amplicons to the 2p24 and 12q13-q14 chromosomal regions. Based on the copy number array data, we sublocalized the minimum common regions of 2p24 and 12q13-q14 amplification to a 0.83 Mb region containing the DDX1 and MYCN genes, and a 0.55 Mb region containing 27 genes, respectively. Using fluorescent in situ hybridization assays to measure copy number of the 2p24 and 12q13-q14 regions in over 100 cases, we detected these amplicons in 13% and 12% of cases, respectively. Comparison with fusion status revealed that 2p24 amplification occurred preferentially in cases positive for PAX3-FOXO1 or PAX7-FOXO1 while 12q13-q14 amplification occurred preferentially in PAX3-FOXO1-positive cases. expression studies demonstrated that MYCN was usuallyoverexpressed in cases with 2p24 amplification while multiple genes were overexpressed in cases with 12q13-q14 amplification. Finally, although 2p24 amplification did not have a significant association with clinical outcome, 12q13-q14 amplification was associated with significantly worse failure-free andoverall survival that was independent of gene fusion status.