The neuroblastoma amplified gene, NAG : genomic structure and characterisation of the 7.3 kb transcript predominantly expressed in neuroblastoma

Scott, Debbie K.; Board, Julian; Lü, Xiaohong; Pearson, Andrew D.J.; Kenyon, R. M.; Lunec, John

doi:10.1016/s0378-1119(03)00459-1

Cited by 29 publications

(24 citation statements)

References 22 publications

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“…The NAG tended toward a more frequent co-ampliWcation with MYCN in stage 4 compared with other stages, in contrast to the result of a signiWcant association of NAG co-ampliWcation with low-stage disease by Scott et al (2003b). The diVerence was probably caused by the lower frequency of NAG co-ampliWcation with MYCN.…”

Section: Overall Survivalmentioning

confidence: 73%

“…They proposed that probes for Southern blot or FISH studies, or primers used for PCR-based methods, should include the 3Ј end of the NAG gene over 400 kb away from DDX1 (Scott et al 2003b). The primers and TaqMan probe we designed were located on the 3Ј end of the NAG gene, on exon 52, and the frequency of NAG co-ampliWcation with MYCN was in accordance with that reported by Scott et al It is thought that a low copy number of MYCN in MYCN-ampliWed human NB cells is correlated with a low degree of recombination and large amplicon size (Amler and Schwab 1989).…”

Section: Overall Survivalmentioning

confidence: 99%

“…Recently, Scott et al reported that the 5Јend of NAG is located 30 kb telomeric to DDX1, with the two genes lying in opposite orientations (Scott et al 2003b). They found a signiWcant association between low-disease stage in MYCN-ampliWed tumors and NAG co-ampliWcation.…”

Section: Introductionmentioning

confidence: 99%

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Relationship of DDX1 and NAG gene amplification/overexpression to the prognosis of patients with MYCN-amplified neuroblastoma

Kaneko

Ohira

Nakamura

et al. 2006

J Cancer Res Clin Oncol

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Section: Overall Survivalmentioning

confidence: 73%

Section: Overall Survivalmentioning

confidence: 99%

See 1 more Smart Citation

Relationship of DDX1 and NAG gene amplification/overexpression to the prognosis of patients with MYCN-amplified neuroblastoma

Kaneko

Ohira

Nakamura

et al. 2006

J Cancer Res Clin Oncol

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“…comm.). This gene was previously found to be amplified in human neuroblastomas (Wimmer et al 1999;Scott et al 2003), but its function is not currently known. All WD repeat-containing proteins share a common function of coordinating multiprotein complex assemblies, forming a scaffold for protein-protein interactions (for review, see Smith et al 1999).…”

Section: Newly Identified Nmd Factors Are Functionally Conserved In Hmentioning

confidence: 99%

Mechanistic insights and identification of two novel factors in the C. elegans NMD pathway

Longman¹,

Plasterk²,

Johnstone³

et al. 2007

Genes Dev.

149

187

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The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons (PTCs). Seven genes (smg-1-7, for suppressor with morphological effect on genitalia) that are essential for NMD were originally identified in the nematode Caenorhabditis elegans, and orthologs of these genes have been found in several species. Whereas in humans NMD is linked to splicing, PTC definition occurs independently of exon boundaries in Drosophila. Here, we have conducted an analysis of the cis-acting sequences and trans-acting factors that are required for NMD in C. elegans. We show that a PTC codon is defined independently of introns in C. elegans and, consequently, components of the exon junction complex (EJC) are dispensable for NMD. We also show a distance-dependent effect, whereby PTCs that are closer to the 3 end of the mRNA are less sensitive to NMD. We also provide evidence for the existence of previously unidentified components of the NMD pathway that, unlike known smg genes, are essential for viability in C. elegans. A genome-wide RNA interference (RNAi) screen resulted in the identification of two such novel NMD genes, which are essential for proper embryonic development, and as such represent a new class of essential NMD genes in C. elegans that we have termed smgl (for smg lethal). We show that the encoded proteins are conserved throughout evolution and are required for NMD in C. elegans and also in human cells.[Keywords: Nonsense-mediated decay; smg genes; RNAi screens; exon junction complex; C. elegans] Supplemental material is available at http://www.genesdev.org. Nonsense-mediated mRNA decay (NMD) is a highly conserved surveillance mechanism present in all eukaryotes examined that prevents the synthesis of truncated proteins. It does so by promoting the degradation of mRNAs containing premature translation termination codons (PTCs) (for a recent review, see Maquat 2004). The functional importance of NMD is highlighted by the fact that this pathway targets for degradation a wide array of endogenous transcripts, as well as erroneously processed transcripts and transcripts carrying spontaneous mutations (for review, see Rehwinkel et al. 2006). It is proposed that NMD modulates the phenotypic outcome of many diseases, since ∼30% of inherited genetic disorders are caused by frameshift or nonsense mutations that generate premature termination codons (PTCs). Therefore, effectors of NMD are potential targets for therapeutic intervention (Frischmeyer and Dietz 1999;Holbrook et al. 2004).Genetic screens in the nematode Caenorhabditis elegans identified seven genes that are required for the degradation of nonsense mutant mRNAs of the unc-54 myosin heavy chain gene (Hodgkin et al. 1989;Pulak and Anderson 1993;Cali et al. 1999). In addition to their suppression-of-unc phenotype, these mutations cause abnormal morphogenesis of the male bursa and the hermaphrodite vulva, and accordingly these genes were termed smg-1-7 (for suppressor with morphological effect on genitalia). In the yeast Sac...

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“…Through a detailed characterization of the molecular structure of the break points involved in this translocation, we have identified a novel chimeric transcript consisting of the neuroblastoma-amplified gene (NAG) 12,13 at 2p24.3 and the engulfment cell motility gene 1 (ELMO1) 14 at 7p14.2. The expression of NAG-ELMO1, in which the 3¢ terminal of ELMO1 was truncated as a result of a frameshift caused by the chromosomal translocation, was detected.…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning of t(2;7)(p24.3;p14.2), a novel chromosomal translocation in myelodysplastic syndrome-derived acute myeloid leukemia

et al. 2009

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In this study, we report the molecular structure of the breakpoint region in a new chromosomal translocation, t(2;7)(p24.3;p14.2), in a case of acute myeloid leukemia transformed from myelodysplastic syndrome (MDS). An extensive fluorescence in situ hybridization (FISH) analysis showed that NAG (2p24.3) and ELMO1 (7p14.2) were involved at the breakpoints of t(2;7)(p24.3;p14.2). Furthermore, we detected a novel chimeric transcript consisting of NAG and ELMO1. Interestingly, this transcript encoded a truncated molecular form of 3¢ELMO1 as the result of a frameshift caused by the chromosomal translocation. Although this study does not provide direct evidence that a defect in NAG-ELMO1 plays a role in the pathogenesis or the leukemic change in MDS, it does suggest that defects in NAG-ELMO1 potentially contributed to the leukemic progression in this case.

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The neuroblastoma amplified gene, NAG : genomic structure and characterisation of the 7.3 kb transcript predominantly expressed in neuroblastoma

Cited by 29 publications

References 22 publications

Relationship of DDX1 and NAG gene amplification/overexpression to the prognosis of patients with MYCN-amplified neuroblastoma

Relationship of DDX1 and NAG gene amplification/overexpression to the prognosis of patients with MYCN-amplified neuroblastoma

Mechanistic insights and identification of two novel factors in the C. elegans NMD pathway

Molecular cloning of t(2;7)(p24.3;p14.2), a novel chromosomal translocation in myelodysplastic syndrome-derived acute myeloid leukemia

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