Co-amplification and concomitant high levels of expression of a DEAD box gene with MYCN in human neuroblastoma

✍ Scribed by Chitra F. Manohar; Helen R. Salwen; Garrett M. Brodeur; Dr. Susan L. Cohn

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 670 KB
• Volume: 14
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/gcc.2870140307

✦ Synopsis

MYCN gene amplification is strongly correlated with poor prognosis in neuroblastoma (NB), the second most common solid pediatric tumor. However, increased MYCN expression seen in tumors that lack MYCN amplification does not correlate with aggressive clinical behavior. Whereas the MYCN gene spans only 7 kb, the MYCN amplicon has been shown t o range in size from 350 kb t o more than I Mb. Given the large size of the amplicon, it is possible that additional genes are co-amplified in NBs whose expression may contribute to the aggressive phenotype associated with MYCN-amplified tumors. We isolated a cDNA clone from a human NB library that is identical t o DDXI, a gene recently reported t o be preferentially expressed in two retinoblastoma cell lines that also express high levels of MYCN. DDXl belongs t o a family of genes that encode DEAD (Asp-Glu-Ala-Asp) box proteins, putative ATP-dependent RNA helicases implicated in a number of cellular processes involving alterations of RNA secondary structure. We examined the frequency of DDXl amplification in I5 N B cell lines, I neuroepithelioma cell line, and I22 NB tumors by Southern blot analyses, and we found that 7 of I 0 MYCN-amplified cell lines and 27 of 40 (68%) MYCN-amplified tumors also harbored multiple copies of the DDXl gene. Amplification of DDXl was associated with high levels of DDXl mRNA expression in the NB cell lines and tumors as examined by Northern analysis. Neither DDXl gene amplification nor enhanced expression was observed in tumors or cell lines that lacked MYCN amplification. Because RNA helicases play important roles in both post-transcriptional and translational gene regulation, high levels of DDX I expression consequent t o genomic amplification may contribute to the malignant phenotype of a subset of NBs. Genes Chromosorn Cancer

14:196-203 (1995).

0 ;995 Wiley-Liss, Inc.