Chromosomal Localization of DNA Amplifications in Neuroblastoma Tumors Using cDNA Microarray Comparative Genomic Hybridization

Beheshti, Ben; Braude, Ilan; Marrano, Paula; Thorner, Paul; Zieleńska, Maria; Squire, Jeremy A.

doi:10.1016/s1476-5586(03)80017-9

Cited by 101 publications

(70 citation statements)

References 45 publications

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Section: Discussionmentioning

confidence: 99%

“…4,5,14,53 A number of highly coamplified regions that were discontinuous regarding the MYCN locus and located at varying distances from MYCN were described, demonstrating the unique constitution of the MYCN amplicon. 4,5,14,53 Interestingly, only one group of researchers found high-level amplification of two genes (SNTG2 and TPO) situated at 936 kb and 1.4 Mb, respectively, from 2pter, occurring in one of 10 MNA samples. 5 In contrast, array expression studies from two independent groups reported the frequent occurrence of elevated expression levels of the genes SH3YL1, 26 ACP1, 49 and RPS7 26,49 situated at 208 kb, 250 kb, and 3.6 Mb, respectively, from 2pter, thus confirming our data.…”

Section: Discussionmentioning

confidence: 99%

“…The size of the MYCN amplicon can extend anywhere from 350 kb to 8 Mb in length, [3][4][5] demonstrating the great variability of amplicon sizes and the number of coamplified genes in NB. A frequently coamplified gene is DDXI (mapping position 2p24), belonging to a family of genes that encode DEAD (Asp-Glu-Ala-Asp) box proteins, implicated in a number of cellular processes, eg, in posttranscriptional and translational gene regulation.…”

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confidence: 99%

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Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

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Bozsaky

Watzinger

et al. 2008

The American Journal of Pathology

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MYCN amplification is associated with poor prognosis in neuroblastoma disease. To improve our understanding of the influence of the MYCN amplicon and its corresponding expression, we investigated the 2p expression pattern of MYCN amplified (n ‫؍‬ 13) and nonamplified (n ‫؍‬ 4) cell lines and corresponding primary tumors (n ‫؍‬ 3) using the comparative expressed sequence hybridization technique. All but one MYCN amplified cell line displayed overexpression at 2p. Expression peaks were observed frequently at 2pter and less frequently at 2p24 (MYCN locus), 2p23.3-23.2, and/or 2p23.1. Importantly, cell lines and two corresponding primary tumors displayed expression peaks at similar loci. No significant 2p24 expression level was observed for those cell lines displaying a low amplification rate (n ‫؍‬ 3) by comparative genomic hybridization. Only the cell lines with an enhanced peak at 2p23.2-23.3 displayed coamplification of the ALK gene (2p23.2), reported to be associated with unfavorable prognosis. Finally, two of four cell lines without MYCN amplification, both derived from patients with poor outcome, also showed an expression peak at 2p23.2. These data indicate that, besides MYCN, other genes proximal and distal to MYCN are highly expressed in neuroblastoma. The prognostic significance of expression peaks at 2p23.2-23.3, independent of MYCN and ALK status, remains to be investigated.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

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Bozsaky

Watzinger

et al. 2008

The American Journal of Pathology

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“…The fluorescence intensity was quantitated by GenePix 3.0 software (Axon Instrument, Union City, CA). Normalization and analysis of microarray data were performed using software developed by Beheshti (19).…”

Section: Methodsmentioning

confidence: 99%

Increased Calcium Influx and Ribosomal Content Correlate with Resistance to Endoplasmic Reticulum Stress-induced Cell Death in Mutant Leukemia Cell Lines

Zhang

Berger²

2004

Journal of Biological Chemistry

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Cell clones were derived by treatment of HL-60 cells with stepwise increasing concentrations of econazole (Ec), an imidazole antifungal that blocks Ca 2؉ influx and induces endoplasmic reticulum (ER) stress-related cell death in multiple mammalian cell types. Clones exhibit 20-to more than 300-fold greater resistance to Ec. Unexpectedly, they also display stable cross-resistance to tunicamycin, thapsigargin, dithiothreitol, and cycloheximide but not doxorubicin, etoposide, or Fas ligand. Phenotypic analysis indicates that the cells display increased store-operated calcium influx and resistance to ER Ca 2؉ store depletion by Ec. E2R2, the most resistant clone, was observed to maintain protein synthesis levels after treatment with Ec or thapsigargin. Expression of GRP78, an ER-based chaperone, was induced by these ER stress treatments but to equal degrees in HL-60 and E2R2 cells. By using microarray analysis, at least 15 ribosomal protein genes were found to be overexpressed in E2R2 compared with HL-60 cells. We also found that ribosomal protein content was increased by 30% in E2R2 as well as other clones. The resistance phenotype was partially reversed by the ribosome-inactivating protein saporin. Therefore, increased store-operated calcium influx, resistance to ER Ca 2؉ store depletion, and overexpression of ribosomal proteins define a novel phenotype of ER stress-associated multidrug resistance.Calcium signals play a central role in many cellular activities including cell movement, secretion, proliferation, gene transcription, and cell death (1, 2). In non-excitable cells, the endoplasmic reticulum (ER) 1 plays a key role in calcium signaling. Receptor-mediated activation of phospholipase C generates the second messenger inositol 1,4,5-triphosphate that diffuses rapidly through the cytosol to interact with inositol 1,4,5-triphosphate receptor on the ER membrane releasing calcium stored in the ER lumen. The resulting depletion of calcium within the ER triggers calcium entry from the extracellular milieu through the plasma membrane. This capacitive or store-operated calcium (SOC) influx (3) serves to both expand the initial calcium signal and replenish the emptied ER store (4, 5). Although the nature of SOC channel remains unclear, the importance of SOC influx in maintaining cell viability has been demonstrated in different studies (6 -13).In addition to its key role in Ca 2ϩ signaling, the ER is a site for protein synthesis, and these two functions intersect under conditions of ER stress. For instance, treatment of cells with thapsigargin (Tg), the inhibitor of the sarcoplasmic/endoplasmic Ca 2ϩ -ATPase responsible for transporting Ca 2ϩ into the ER, rapidly depletes ER Ca 2ϩ stores (14), inhibits the function of Ca 2ϩ -dependent chaperones, and triggers the unfolded protein response (15). Econazole (Ec) is an antifungal imidazole that depletes Ca 2ϩ from the ER of mammalian cells and blocks Ca 2ϩ influx (16, 17). These effects result in sustained depletion of Ca 2ϩ from ER stores and profound inhibition of prot...

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“…Custom software Normalize Suite v1.56 was used for normalization of Cy3 and Cy5 intensities, data combination of dye swap experiments and integration of signal ratios determined with physical map locations of cDNAs in sequential order of megabase distances (http://www.utoronto.ca/cancyto/). 27 …”

Section: Microarray Analysismentioning

confidence: 99%

Positional expression profiling indicates candidate genes in deletion hotspots of hepatocellular carcinoma

et al. 2006

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Molecular characterizations of hepatocellular carcinoma have indicated frequent allelic losses on chromosomes 4q, 8p, 16q and 17p, where the minimal deleted regions have been further defined on 4q12-q23, 4q31-q35, 8p21-p22, 16q12.1-q23.1 and 17p13. Despite these regions are now well-recognized in early liver carcinogenesis, few underlying candidate genes have been identified. In an effort to define affected genes within common deleted loci of hepatocellular carcinoma, we conducted transcriptional mapping by highresolution cDNA microarray analysis. In 20 hepatocellular carcinoma cell lines and 20 primary tumors studied, consistent downregulations of novel transcripts were highlighted throughout the entire genome and within sites of frequent losses. The array-derived candidates including fibrinogen gamma peptide (FGG, at 4q31.3), vitamin D binding protein (at 4q13.3), fibrinogen-like 1 (FGL1, at 8p22), metallothionein 1G (MT1G, at 16q12.2) and alpha-2-plasmin inhibitor (SERPINF2, at 17p13) were confirmed by quantitative reverse transcriptionpolymerase chain reaction, which also indicated a more profound downregulation of FGL1, MT1G and SERPINF2 relative to reported tumor-suppressor genes, such as DLC1 (8p22), E-cadherin (16q22.1) and TP53 (17p13.1). In primary hepatocellular carcinoma examined, a significant repression of MT1G by more than 100-fold was indicated in 63% of tumors compared to the adjacent nonmalignant liver (P ¼ 0.0001). Significant downregulations of FGG, FGL1 and SERPINF2 were also suggested in 30, 23 and 33% of cases, respectively, compared to their nonmalignant counterparts (Po0.016). In summary, transcriptional mapping by microarray indicated a number of previously undescribed downregulated genes in hepatocellular carcinoma, and highlighted potential candidates within common deleted regions. Keywords: hepatocellular carcinoma; deletion hotspots; cDNA array; transcriptional mapping Hepatocellular carcinoma currently ranks the fifth most common malignancy worldwide. 1,2 It carries a high cancer morbidity and mortality because by the time of clinical presentation, more than 80% of patients are at the advance inoperable stage. 2,3 The low efficacy of current screening regime by serum alpha-fetoprotein measurements and transabdominal ultrasound imaging has rendered most patients not being diagnosed in time for curative surgery.Thus, underpinning the genetic events associated with hepatocellular carcinoma is expected to improve our understanding on liver carcinogenesis and also potentially provide biomarkers that are of diagnosis and prognostic values.Molecular studies using loss of heterozygosity analysis and comparative genomic hybridization have revealed recurrent chromosomal changes in hepatocellular carcinoma including losses on 1p, 4q, 6q, 8p, 11q, 13q, 16q and 17p. [4][5][6] As diminutions on 4q, 8p, 16q and 17p have been described in the nontumorous cirrhotic nodules and early preneoplastic liver dysplasia, these changes have been further implicated in the early carcinogenetic events of hepat...

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Chromosomal Localization of DNA Amplifications in Neuroblastoma Tumors Using cDNA Microarray Comparative Genomic Hybridization

Cited by 101 publications

References 45 publications

Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

Increased Calcium Influx and Ribosomal Content Correlate with Resistance to Endoplasmic Reticulum Stress-induced Cell Death in Mutant Leukemia Cell Lines

Positional expression profiling indicates candidate genes in deletion hotspots of hepatocellular carcinoma

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