Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased N-myc (now designated NMYC in human gene nomenclature) gene expression has been detected at the transcriptional level in certain types of neoplasms. As yet, the N-myc gene product has not been identified. To detect and characterize the N-myc gene product, we have developed monoclonal antibodies against the putative N-myc gene product made in Escherichia coli as a fusion protein. The antibodies that recognize the N-myc-specific regions were selected on the basis of their reactivities to different portions of the fusion protein. These monoclonal antibodies detect a pair of closely migrating polypeptides of 60 and 63 kDa in nuclear fractions of human neuroblastoma cells. The relative levels of the polypeptides are roughly proportional to the level of N-myc transcripts present in a panel of neuroblastoma lines. These two polypeptides have a half-life of approximately equal to 35 min, and they are indistinguishable from each other by their epitopic profiles.
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PMID:Identification and characterization of the NMYC gene product in human neuroblastoma cells by monoclonal antibodies with defined specificities. 242 8

Gene amplification in mammalian cells commonly manifests itself as homogeneously staining chromosomal regions (HSRs). These are frequently seen in neuroblastoma and have been shown to be the site of amplification of the NMYC oncogene. We have used a nonisotopic, high-resolution in situ hybridization technique to reveal a hitherto unrecognized periodic microstructure within HSRs of a human neuroblastoma cell line.
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PMID:High-resolution in situ hybridization technique using biotinylated NMYC oncogene probe reveals periodic structure of HSRs in human neuroblastoma. 243 57

By restriction fragment length polymorphism (RFLP) analysis, it was found that loss of heterozygosity (LOH) at three different chromosomal loci, 3p, 13q, and 17p, occurs simultaneously in nearly 100% of small-cell lung carcinomas (SCLC). This was observed even in stage I tumors and an untreated tumor, and it occurred prior to NMYC amplification. The common region of LOH on chromosome 3p was 3p14-24.1, and this region was also frequently lost in carcinoma of the uterine cervix (100% at D3S2 on 3p14-21) as well as renal cell carcinoma (56% at ERBA beta on 3p22-24.1), suggesting the presence of tumor suppressor gene(s) for these cancers in this region. On chromosome 13, LOH was observed commonly in the region between 13q12 and 13q22, including the RB locus on 13q14, and normal RB protein was not detected in any of 9 SCLC cell lines by immunoprecipitation analysis. The common region of LOH on chromosome 17 was 17p13 and is the same as that in colon carcinoma and osteogenic sarcoma. Since LOH is supposed to unmask the recessive mutation of tumor suppressor gene in the remaining allele, these results may imply that at least six genetic alterations are necessary to convert a normal cell into a fully malignant cancer cell in SCLC. RFLP analysis was performed on several other types of human cancers, including carcinoma of the uterine cervix, neuroblastoma, hepatocellular carcinoma, pheochromocytoma, and stomach cancer to determine the chromosomal loci of putative tumor suppressor genes in each tumor. Chromosomal loci showing frequent LOH were different among these tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple genetic alterations in small-cell lung carcinoma. 257 37

Members of the MYC gene family, including MYC, NMYC, and LYMC, have been found amplified and expressed at high level in various human cancers. We have analysed the expression of two members of the MYC gene family, NMYC and MYC, in human and murine neuroblastoma cells. Whenever NMYC and MYC are co-expressed, MYC expression predominates. Cells carrying high expression of NMYC as result of amplification lack MYC expression. The same is ture for neuroblastoma cells in which expression of a single-copy NMYC is upregulated or into which a vector forcing high expression of an exogenous NMYC had been introduced by transfection. Our studies indicate a regulatory interaction between MYC and NMYC in neuroblastoma cells.
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PMID:Suppression of MYC by high expression of NMYC in human neuroblastoma cells. 281 Mar 95

Recently an amplification of NMYC oncogene was discovered in stage III and stage IV as well as in stage II neuroblastoma cells. The extent of NMYC amplification is of prognostic value. A high expression of NMYC on mRNA level is correlated to the NMYC gene-amplification. We utilized the in situ-hybridization technique for the detection of NMYC-mRNA expression on cellular level, and the Southern Blot method for analysing the total genomic DNA. In three stage IV patients with overt neuroblastoma in bone marrow cells, NMYC gene-amplification as well as NMYC-mRNA were detected. Seven control bone marrows of patients with different heamatological diseases in different stages did not contain positive cells in our in situ-hybridization assay.
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PMID:[Detection of neuroblastoma cells in bone marrow by Southern blot and in situ hybridization using a NMYC DNA probe]. 360 Jun 72

Using a mouse cDNA probe for ornithine decarboxylase (ODC), we have identified and isolated an ODC cDNA clone from a lambda gt11 recombinant library prepared from human liver cell mRNA. The 2.0-kb insert of this clone hybridizes with several mouse genomic ODC DNA restriction fragments under conditions of low stringency, but reacts with only few human DNA fragments and a polyA+ RNA species of 2.2 kb under both nonstringent and stringent hybridization conditions. This suggests that, unlike the mouse genome, there are only few ODC genes in the human genome. The human ODC DNA fragments segregate with chromosome regions 2pter----p23 and 7cen----qter in mouse X human somatic cell hybrid clones containing normal, translocated, and deleted human chromosomes. Sequences of the short arm of chromosome 2 containing the NMYC oncogene at 2p23----p24 are often involved in DNA amplification in neuroblastomas and small-cell lung cancers. However, in at least three cases--one neuroblastoma cell line, one neuroblastoma tumor, and one lung carcinoma--the ODC sequences are not coamplified with the NMYC oncogene.
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PMID:Human ornithine decarboxylase sequences map to chromosome regions 2pter----p23 and 7cen----qter but are not coamplified with the NMYC oncogene. 375 88

The short arm of chromosome 1p is the most frequently altered chromosome segment in neuroblastoma. The alterations, mainly deletions, are thought to be indicative of the presence of a tumor suppressor gene. To further refine the chromosome localization of this gene, we have studied paired constitutional and tumor DNA from a series of 60 patients with neuroblastoma at 2 minisatellite and 23 microsatellite loci dispersed along the short arm of chromosome 1. Twenty-two cases (37%) demonstrated loss of heterozygosity (LOH) at one or more loci on 1p. Surprisingly, the pattern of LOH enabled the identification of two distinct consensus regions of deletions. In agreement with previous reports, one region mapped to the distal short arm of chromosome 1. The other region was localized more proximally on 1p. Deletions observed in tumors involve either one or both of these regions. We show that the correlation between NMYC amplification and 1p deletion is limited to the deletions which involve the proximal region either alone or together with the distal region. These results suggest that two tumor suppressor genes on 1p might be involved in the development of neuroblastoma. Finally, we show that somatic mutations at microsatellite loci, frequently observed in other types of cancer, are rare events in neuroblastoma.
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PMID:Two distinct deleted regions on the short arm of chromosome 1 in neuroblastoma. 752 42

HMGI-C and HMGI(Y) are architectural DNA-binding proteins that participate in the conformational regulation of active chromatin. Their pattern of expression in embryonal and adult tissues, the analysis of the "pygmy" phenotype induced by the inactivation of the HMGI-C gene, and their frequent qualitative or quantitative alteration in experimental and human tumors indicate their pivotal role in the control of cell growth, differentiation, and tumorigenesis in several tissues representative of the epithelial, mesenchymal, and hematopoietic lineages. In contrast, very little information is available on their expression and function in neural cells. Here, we investigated the expression of the HMGI(Y) and HMGI-C genes in neuroblastoma (NB), a tumor arising from an alteration of the normal differentiation of neural crest-derived cells and in embryonal and adult adrenal tissue. Although HMGI(Y) is constitutively expressed in the embryonal and adult adrenal gland and in all of the NB cell lines and ex vivo tumors examined, its regulation appears to be associated to growth inhibition and differentiation because we observed that HMGI(Y) expression is reduced by retinoic acid (RA) in several NB cell lines that are induced to differentiate into postmitotic neurons, whereas it is up-regulated by RA in cells that fail to differentiate. Furthermore, the decrease of HMGI(Y) expression observed in RA-induced growth arrest and differentiation is abrogated in cells that have been made insensitive to this drug by NMYC overexpression. In contrast, HMGI-C expression is down-regulated during the development of the adrenal gland, completely absent in the adult individual, and only detectable in a subset of ex vivo NB tumors and in RA-resistant NB cell lines. We provide evidence of a causal link between HMGI-C expression and resistance to the growth arrest induced by RA in NB cell lines because exogenous HMGI-C expression in HMGI-C-negative and RA-sensitive cells is sufficient to convert them into RA-resistant cells. Therefore, we suggest that HMGI-C and HMGI(Y) may participate in growth- and differentiation-related tumor progression events of neuroectodermal derivatives.
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PMID:HMGI(Y) and HMGI-C genes are expressed in neuroblastoma cell lines and tumors and affect retinoic acid responsiveness. 1034 62

Neuroblastoma, the most common extracranial solid tumor of childhood, is associated with a number of genetic abnormalities that are prognostically significant. The most common abnormalities are associated with aggressive clinical behavior and include deletion of distal chromosome 1p, NMYC amplification, and unbalanced gain of the long arm of chromosome 17. There are also other recurrent, but less frequent abnormalities, the clinical significance of which is uncertain. These less common abnormalities include deletion 3p, 11q, and 14q. To gain further clinical insight into some of the less commonly observed abnormalities in neuroblastoma, we performed comparative genomic hybridization (CGH) analysis on 24 primary and metastatic neuroblastomas (6 stage 2, 5 stage 3, 11 stage 4, and 2 stage 4). Nineteen of these tumors were prechemotherapy. A total of 190 abnormalities were detected from these tumors. Four of the 24 tumors studied showed loss of 11q material, with 3 of these tumors also possessing distal chromosome 3p deletions. Our results provide confirmation that deletion of chromosome 3p is nonrandomly associated with deletion of chromosome 11q in neuroblastoma. However, analysis of our results, along with other results reported in the literature, indicate that there is no statistically significant association between 3p and 11q loss and more clinically aggressive tumors.
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PMID:Coordinate deletion of chromosome 3p and 11q in neuroblastoma detected by comparative genomic hybridization. 1091 76

We developed an antisense peptide nucleic acid (PNA) targeted against a unique sequence in the terminus of the 5'-UTR of N-myc, designed for selective inhibition of NMYC in neuroblastoma cells. Fluorescent microscopy showed carrier-free delivery of the PNA to two human neuro-blastoma cell lines: GI-LI-N (N-myc-amplified) and GI-CA-N (N-myc-unamplified). Only in the former, PNA treatment determined 70% cell-viability reduction (at 48 h). In N-myc-amplified GI-LI-N cells, the PNA determined NMYC-translation inhibition (Western blotting), accumulation of cells in G1, induction of differentiation and apoptosis. Selectivity of the PNA was demonstrated by altering three point mutations. These findings should encourage development of a PNA-based tumor-specific agent for neuroblastoma (or other neoplasms) with N-myc overexpression.
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PMID:Targeted inhibition of NMYC by peptide nucleic acid in N-myc amplified human neuroblastoma cells: cell-cycle inhibition with induction of neuronal cell differentiation and apoptosis. 1471 1


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