Co-amplification of a novel gene, NAG, with the N-myc gene in neuroblastoma

Wimmer, Katharina; Zhu, Xiaoxiang; Lamb, BJ; Kuick, Rork; Ambros, Peter F.; Kovar, Heinrich; Thoraval, Didier; Motyka, Stephanie; Alberts, JR; Hanash, SM

doi:10.1038/sj.onc.1202287

Cited by 70 publications

(54 citation statements)

References 32 publications

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“…Amplification of DDX1 and NAG was found in half and onethird of nearly 100 MNA NB samples, respectively. These findings are in keeping with the literature data with the exception of a higher NAG coamplification percentage in a study by Wimmer and colleagues (14), which might be explained by the small number of tumors tested in their study. Kaplan Meier survival analysis demonstrated that DDX1 or NAG co-amplification did not result in additional unfavorable prognostic effect.…”

Section: Discussionsupporting

confidence: 92%

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Quantification of MYCN, DDX1, and NAG Gene Copy Number in Neuroblastoma Using a Real-Time Quantitative PCR Assay

et al. 2002

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Amplification of the proto-oncogene MYCN is a strong adverse prognostic factor in neuroblastoma patients in all tumor stages. The status of the MYCN gene has become an important factor in clinical decision making and therapy stratification. Consequently, fast and accurate assessment of MYCN gene copy number is of the utmost importance and the use of two independent methods to determine MYCN status is recommended. For these reasons we have developed and evaluated a real-time quantitative PCR (Q-PCR) assay as an alternative for timeconsuming Southern blot analysis (SB), and as a second independent technique in parallel with fluorescence in situ hybridization (FISH) analysis. Advantages of Q-PCR are a large dynamic range of quantification, no requirement for post-PCR sample handling and the need for very small amounts of starting material. The accuracy of the assay was illustrated by measurement of MYCN single gene copy changes in DNA samples of two patients with 2p deletion and duplication, respectively. Two different detection chemistries i.e., a sequence specific TaqMan probe and a generic DNA binding dye SYBR Green I were evaluated and shown to yield similar results. Also, two different calculation methods for copy number determination were used i.e., the kinetic method and the comparative C T method, and shown to be equivalent. In total, 175 neuroblastoma samples with known MYCN status, as determined by FISH and/or SB, were examined. Q-PCR data were highly concordant with FISH and SB data. In addition to MYCN copy number evaluation, DDX1 and NAG gene copy numbers were determined using a similar Q-PCR strategy. Survival analysis pointed out that DDX1 and/or NAG amplification has no additional adverse effect on prognosis.

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Section: Discussionsupporting

confidence: 92%

“…In addition we determined the copy number of DDX1 and NAG. Both genes are known to be co-amplified in subsets of MYCN amplified tumors (11)(12)(13)(14). The copy numbers of the two latter genes were used to determine a possible correlation of co-amplification with survival and risk to relapse of the patient.…”

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confidence: 99%

Quantification of MYCN, DDX1, and NAG Gene Copy Number in Neuroblastoma Using a Real-Time Quantitative PCR Assay

et al. 2002

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“…The size of the N-myc amplicons varies among cell lines to over 1 Mb, including approximately 7 kb of the N-myc gene (Akiyama et al, 1994;Hiemstra et al, 1994). Additionally, contribution of genes co-amplified with N-myc to cancer progression was also proposed (George et al, 1996;Wimmer et al, 1999). Since no information about range of amplification or exact distance between ALK and N-myc loci was obtained, we could not conclude that a single amplicon contains both of these genes.…”

Section: Discussionmentioning

confidence: 74%

Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines

Hakomori²,

et al. 2002

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“…One of these proteins was CSN3, a member of the CSN complex (24). The second interacting protein was encoded by the neuroblastomaassociated gene and was not further characterized (26).…”

Section: Yeast Two-hybrid Screens With Icil-1ra Isoformsmentioning

confidence: 99%

Intracellular IL-1 Receptor Antagonist Type 1 Inhibits IL-1-Induced Cytokine Production in Keratinocytes through Binding to the Third Component of the COP9 Signalosome

Banda

Guthridge

Sheppard

et al. 2005

The Journal of Immunology

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The IL-1 receptor antagonist (IL-1Ra) exists in four isoforms, three of which lack signal peptides and are primarily intracellular proteins. The biologic roles of the intracellular isoforms of IL-1Ra have remained unknown. The objective of these studies was to determine whether the major intracellular isoform of IL-1Ra 18-kDa type 1 (icIL-1Ra1), mediated unique functions inside cells. A yeast two-hybrid screen with HeLa cell lysates revealed specific binding of icIL-1Ra1, and not of the other IL-1Ra isoforms, to the third component of the COP9 signalosome complex (CSN3). This binding was confirmed by Far Western blot analysis, sedimentation on a glycerol gradient, glutathione pull-down experiments, and coimmunoprecipitation. In addition to binding specifically to CSN3, icIL-1Ra1 inhibited phosphorylation of p53, c-Jun, and IκB by the crude CSN-associated kinase and of p53 by recombinant protein kinase CK2 and protein kinase D, both associated with CSN3. The biologic relevance of the interaction between icIL-1Ra1 and CSN3 was demonstrated in the keratinocyte cell lines KB and A431, both possessing abundant CSN3. A431 cells exhibited high levels of icIL-1Ra1 but lacked both detectable IL-1α-induced IL-6 and IL-8 production and phosphorylation of p38 MAPK. KB cells displayed the opposite pattern which was reversed after transfection with icIL-1Ra1 mRNA. Inhibition of CSN3 or of icIL-1Ra1 production through gene knockdown with specific small interfering RNA in A431 cells each led to an inhibition of IL-1α-induced IL-6 and IL-8 production. Thus, icIL-1Ra1 exhibits unique anti-inflammatory properties inside cells through binding to CSN3 with subsequent inhibition of the p38 MAPK signal transduction pathway.

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Co-amplification of a novel gene, NAG, with the N-myc gene in neuroblastoma

Cited by 70 publications

References 32 publications

Quantification of MYCN, DDX1, and NAG Gene Copy Number in Neuroblastoma Using a Real-Time Quantitative PCR Assay

Quantification of MYCN, DDX1, and NAG Gene Copy Number in Neuroblastoma Using a Real-Time Quantitative PCR Assay

Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines

Intracellular IL-1 Receptor Antagonist Type 1 Inhibits IL-1-Induced Cytokine Production in Keratinocytes through Binding to the Third Component of the COP9 Signalosome

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