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)

We have used the polymerase chain reaction (PCR) to detect amplification of the MYCN oncogene in neuroblastoma cell lines and to distinguish primary tumors with a single copy from those with MYCN amplification using DNA extracted from frozen sections. Two primer pairs were used to co-amplify a 428-bp fragment of the MYCN oncogene along with a 268-bp fragment of the beta-globin gene (a single-copy reference standard). After 30 cycles of PCR, the products were resolved by agarose gel electrophoresis. MYCN gene amplification was identified by visual comparison of the relative intensities of MYCN and beta-globin PCR product bands on the ethidium bromide-stained gel. This semiquantitative approach, while inadequate for precise determination of copy number, provided a simple, rapid, nonisotopic method for differentiating tumors with MYCN amplification from those with a single copy. Seventy-four primary tumors were classified as amplified or nonamplified by semiquantitative PCR. Twenty-two of 23 tumors known to carry MYCN gene amplification by Southern analysis were correctly identified by PCR. The single false-negative result was due to a sampling error: DNA was extracted from a block of tissue containing small foci of tumor surrounded by normal tissue. Fifty-one of 51 tumors with a single copy of MYCN were also correctly identified by PCR. We conclude that semiquantitative PCR is a reliable, non-isotopic alternative to Southern blotting for detection of MYCN gene amplification that can be performed rapidly on DNA extracted from frozen sections.
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PMID:Rapid detection of MYCN gene amplification in neuroblastomas using the polymerase chain reaction. 134 70

An unambiguous and rapid characterization of amplified DNA sequences in tumor cells is important for the understanding of neoplastic progression. This study was conducted to evaluate the potential of fluorescence in situ hybridization (FISH) to identify such amplified DNA sequences in human tumor cell lines. Applying this technique, we followed the metaphase location and interphase position of amplified DNA sequences corresponding to the SAMK, MYC, and MYCN genes in four cell lines derived from human tumors: two gastric carcinoma lines (KATO III and SNU-16), a neuroblastoma (NUB-7), and a neuroepithelioma (NUB-20) line. In metaphase cells of KATO III, NUB-7, and NUB-20 lines, the amplified regions were clearly visible and easily identified at an intrachromosomal location: in KATO III and NUB-7 at a terminal position and in NUB-20 at an interstitial position. In SNU-16, on the other hand, the amplified SAMK and MYC sequences were identified in extrachromosomal double minute chromosomes (DMs). In this line, the SAMK and MYC sequences were coamplified in the same cells and were colocated on the same DMs. FISH also allowed the identification of amplified DNA sequences in nondividing cells, enabling us to distinguish, at interphase, whether the amplification gave rise to intrachromosomal amplified regions (IARs) or to extrachromosomal DMs. The FISH technique also allowed us to determine at metaphase as well as at interphase the extent of amplification and the size of the IARs.
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PMID:Detection of amplified DNA sequences in human tumor cell lines by fluorescence in situ hybridization. 137 38

Three neuroblastoma cell lines established from tumor samples obtained from one patient are described. The three lines were derived from bone marrow aspirates taken at diagnosis, and 13 and 15 months later. The origin of the cell lines PER-106, PER-107, and PER-108 from malignant neuroblasts was confirmed by electron microscopy studies, surface marker analysis, and assessment of MYCN amplification. Cell lines PER-107 and PER-108, which were established from tumor samples obtained at the time of progressive disease, have significantly shorter doubling times than PER-106 and grow mainly substrate-adherent, while cell line PER-106 (established from sample obtained at diagnosis) consists of small round neuroblastic cells which form large aggregates in suspension culture. The electron microscopy studies revealed distinctive neuroblast-like ultrastructure in all cell lines. The MYCN copy number was amplified (greater than 10 copies) in the established cell lines and in the fresh tumor samples and the relative abundance of MYCN RNA in the cell lines correlated roughly with the extent of the MYCN gene amplification. However, distinct phenotypic differences can be demonstrated among these three lines, which provide a model for the further examination of this highly malignant tumor. Detection of MYCN amplification by chromosomal in situ hybridization was performed on this set of cell lines, as reported by McRobert et al. (this issue, pages 128-134).
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PMID:Three neuroblastoma cell lines established from consecutive samples of one patient which show distinct morphologic features, MYCN amplification, and surface marker expression. 158 78

A non-radioactive chromosomal in situ hybridization technique utilizing a biotin-streptavidin-polyalkaline-phosphatase complex was successfully applied to three neuroblastoma cell lines for detection of MYCN amplification. These cell lines, designated PER-106, PER-107, and PER-108, were derived from consecutive bone marrow samples taken from a patient with stage IV neuroblastoma. The cell line derived at diagnosis (PER-106) exhibited MYCN amplification in the form of variable numbers of double-minute chromosomes, small fragments, and rings of varying sizes. This observed variability of MYCN amplification may explain the reported heterogeneity of both MYCN mRNA and protein expression among individual cells of some neuroblastomas. The cell lines derived from subsequent samples (PER-107 and PER-108) contained amplified MYCN as two consistent homogeneously staining regions in every cell. These were located on the short arms of chromosomes 6 and 14. Thus, amplified MYCN was identified in each cell line and demonstrated the concurrent evolution of amplification with cytogenetic abnormalities.
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PMID:Detection of MYCN amplification in three neuroblastoma cell lines by non-radioactive chromosomal in situ hybridization. 158 79

We have examined the effect of human basic fibroblast growth factor (bFGF) on the proliferation of human neuroblastoma cells with normal and enhanced MYCN oncogene expression. bFGF stimulated the proliferation of the neuroblastoma cells with enhanced, but not normal, MYCN expression. Both cell species express FGFR-1, but not FGFR-2, receptors and both harbor FGF receptor species of Mr 145.000, but they differ in their pattern of lower and higher-molecular weight FGF receptor species. Our results demonstrate that enhanced MYCN expression confers to neuroblastoma cells the ability to respond to bFGF, possibly by inducing functional FGF receptors. This mechanism may contribute to the advanced malignant phenotype of human neuroblastomas with enhanced MYCN expression.
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PMID:Enhanced MYCN oncogene expression in human neuroblastoma cells is associated with altered FGF receptor expression and cellular growth response to basic FGF. 165 53

Human neuroblastoma cells often carry non-random chromosomal abnormalities signalling genetic alterations. Quite frequent are 'double minutes' (DMs) and homogeneously staining regions (HSRs), both cytogenetic manifestations of amplified DNA, and chromosome 1p-deletions indicating loss of genetic information. With the identification of amplified MYCN and the demonstration of a consensus deletion spanning the chromosome 1p36.1-2 region it appears now likely that both amplification of a cellular oncogene and loss of a tumour-suppressor gene play an important role in neuroblastoma. Amplification of MYCN is an indicator for poor prognosis, even when classical morphological criteria would suggest a better outcome. Consequently, patients with amplification are subjected to more intensive therapeutic regimens. Amplification of MYCN is a paradigm for the clinical use of an oncogene alteration.
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PMID:Amplification of the MYCN oncogene and deletion of putative tumour suppressor gene in human neuroblastomas. 166 92

At least two genetic events have been identified which are characteristic of certain neuroblastomas. These are loss of a critical region on the short arm of chromosome 1, and amplification of the MYCN proto-oncogene. Our studies suggest that the two genetic events may be related, and that loss of heterozygosity (LOH) for chromosome 1p may precede the development of amplification. RAS gene mutations appear to be rare, and no other oncogene has been shown to be consistently activated by amplification or other mechanism. LOH for chromosome 14q has been identified recently, but its frequency and significance is not clear. Based on flow cytometric analysis of DNA content, tumour cytogenetics and molecular studies, three distinct genetic subsets of neuroblastomas are emerging. The first is characterized by a hyperdiploid or near-triploid modal karyotype, with few if any cytogenetic rearrangements. These patients are generally less than one year of age with localized disease and a good prognosis. The second group is characterized by a near-diploid or near-tetraploid karyotype, with no consistent rearrangement identified to date. They are generally older patients with more advanced stages of disease that progress slowly and are ultimately fatal. The third group is characterized by a near-diploid or tetraploid karyotype, with deletions or LOH for chromosome 1p, amplification of MYCN, or both. These patients are generally older with advanced stages of disease which is rapidly progressive. Thus, genetic analysis of neuroblastoma cells by karyotype, flow cytometry and determination of MYCN copy number provides information that has prognostic significance and can more appropriately direct the choice of treatment. A better understanding of these genetic abnormalities and the biochemical pathways that they effect may provide insights into malignant transformation and progression, as well as provide targets for future therapeutic approaches.
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PMID:Neuroblastoma--clinical applications of molecular parameters. 166 93

LFA-3, ICAM-1, HLA.ABC and HLA.DR expression was analyzed on 66 neuroblastoma specimens. HLA.ABC was expressed on 26 specimens, HLA.DR on 2, LFA-3 on 20 and ICAM-1 on 10. HLA.ABC and LFA-3 were positive on ganglioneuroblastoma or ganglioneuroma, but they were negative on neuroblastoma, independently of the clinical staging; HLA.ABC and LFA-3 were induced in vivo by chemotherapy in parallel with tumoral cell differentiation, in both the primary and the metastases. The expression of ICAM-1 was restricted to 5 of the 10 low-grade stage-1 or stage-2 specimens, 1 stage-3 specimen, and the primary tumors of 2 patients with stage-4 disease, analyzed hence at diagnosis and after chemotherapy (4 specimens); metastatic cells obtained in 1 of these patients were negative. HLA.ABC and LFA-3 expressed on both mycN-negative and -positive specimens, whereas ICAM-1 was restricted to MYCN-negative specimens. LFA-3 diffusely stained partially differentiated neuroblasts, Schwann cells and ganglion cells. The expression of HLA.ABC on differentiated neuroblasts varied from one sample to another and within the same tumor; Schwann cells were strongly positive, but ganglion cells were negative. In positive samples, ICAM-1 was expressed on differentiated neuroblasts and Schwann cells, but negative on ganglion cells; however, most of the differentiated tumors were ICAM-1-negative, suggesting ICAM-1 induction by unknown local signal. The 4 markers were negative on undifferentiated neuroblasts. The distribution of these 4 markers on clinical specimens was in agreement with their reactivity on fetal tissues, as well as with results obtained on neuroblastoma cell lines before and after in vitro treatment with IFN-gamma.
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PMID:Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens. 171 Jun 8

The effects of an antisense oligodeoxynucleotide to codons 2-7 of the oncogene MYCN on the human neuroblastoma cell line LAN-5 were studied. Treated cells showed a decreased MYCN protein expression and synthesis by immunoperoxidase staining and immunoprecipitation. At the same time, the replication rate was inhibited, and the phenotype was modified toward a more differentiated type. Our data suggest the involvement of oncogene MYCN in both proliferative and differentiative processes.
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PMID:Decrease of proliferation rate and induction of differentiation by a MYCN antisense DNA oligomer in a human neuroblastoma cell line. 175 6

Tumors of the peripheral nervous system include neuroblastomas, pheochromocytomas, and neuroepitheliomas. Neuroblastomas and pheochromocytomas are adrenergic in origin and share certain genetic features, whereas neuroepitheliomas are thought to be cholinergic and are characterized by distinct genetic features. Neuroblastomas are characterized by deletion of the short arm of chromosome 1 (1p), amplification of the MYCN proto-oncogene, and hyperdiploidy in subsets of tumors. All three of these genetic features have prognostic value in subsets of patients. Allelic loss of 14q also occurs with increased frequency, but the prognostic importance of this abnormality is not known yet. Pheochromocytomas have not been studied as extensively, but allelic loss for 1p appears to be a frequent change, and no clear examples of oncogene activation have been identified to date. Neuroepitheliomas are characterized by translocation between chromosomes 11 and 22. Although they have a characteristic pattern of proto-oncogene expression, it is not clear that any of these oncogenes are activated specifically, and no sites of allelic loss have been identified to date. Thus, cytogenetic and molecular analysis of neuroblastomas, pheochromocytomas, and neuroepitheliomas are useful in distinguishing them from each other and from other tumors in selected cases. Furthermore, certain genetic markers are useful in predicting clinical behavior, especially for neuroblastoma.
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PMID:Biology of tumors of the peripheral nervous system. 178 33


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