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)

Band 1p36.1-1p36.2 is frequently involved in chromosomal aberrations of neuroblastoma cells, and therefore thought to harbour genetic information which may be involved in tumorigenesis. To map this putative neuroblastoma locus, we screened neuroblastoma cell lines for reciprocal translocations at 1p36.1-2 which may signal the site of an affected gene. We identified a reciprocal 1;15 translocation in cell line NGP by fluorescence in situ hybridisation (FISH). As a strategy to clone the translocation breakpoint, we isolated yeast artificial chromosomes (YACs) specific for loci at 1p36. Screening of cell line NGP by FISH identified a YAC, 1050 kbp in size, which hybridised to both derivative 1;15 and 15;1 chromosomes. We conclude that this YAC, which maps to D1S160, covers the break. This chromosomal position is within the smallest region of overlap (SRO) found in neuroblastoma tumours and within the region of a constitutional interstitial deletion of a neuroblastoma patient. The YAC we describe here should serve as a DNA source for gene cloning approaches towards the isolation of candidates for the putative neuroblastoma suppressor gene.
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PMID:Reciprocal translocation at 1p36.2/D1S160 in a neuroblastoma cell line: isolation of a YAC clone at the break. 757 59

Telomerase activity was analysed in 100 neuroblastoma cases. Although telomerase activity was not detected in normal adrenal tissues or benign ganglioneuromas, almost all neuroblastomas (94%) did express it, suggesting an important role for telomerase in neuroblastoma development. Neuroblastomas with high telomerase activity had other genetic changes (for example, N-myc amplification) and an unfavourable prognosis, whereas tumours with low telomerase activity were devoid of such genetic alterations and were associated with a favourable prognosis. Three neuroblastomas lacking telomerase activity regressed (stage IVS). Thus telomerase expression may be required as a critical step in the multigenetic process of tumorigenesis, and two different pathways may exist for the development of neuroblastoma.
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PMID:Correlating telomerase activity levels with human neuroblastoma outcomes. 758 30

We have analyzed DNA from 46 neuroblastoma tumors of all clinical stages and five ganglioneuroma tumors together with corresponding control DNA for loss of heterozygosity (LOH) on the distal 1p chromosomal region (1p-LOH). The markers used for the analyses were genetically mapped DNA polymorphisms detectable with PCR analysis. In general, there was concordance among aggressive tumor stage, 1p deletion, and N-myc amplification, although exceptions were found. Twelve (26%) of the 46 neuroblastoma tumors displayed 1p-LOH, 11 being stage 4 and 1 stage 2 (which progressed subsequently to stage 4), whereas 10 stage 4 tumors showed no 1p-LOH. Of 12 neuroblastomas shown to have N-myc amplification, 10 had 1p-LOH. In 8 cases it was possible to test for parental origin of the chromosome involved in 1p-LOH. No significant correlation between LOH and paternal or maternal allele was found. Commonly deleted loci in the distal 1p region in the neuroblastoma tumors indicated that the region for a tentative neuroblastoma tumor suppressor gene is defined proximally by marker D1S244 and distally by marker D1S80. One striking feature of three stage 2 neuroblastomas and one of the stage 3 tumors was the presence in the tumor DNA of alleles not present in the constitutional DNA of the patients, i.e., microsatellite instability. The significance of this phenomenon in localized neuroblastoma tumors remains to be clarified. Aggressive neuroblastoma in young children (younger than 2 years of age) seems to be a homogenous disorder consistently showing concomitant 1p-LOH and N-myc amplification. In the majority of unfavorable neuroblastoma in older children, however, neither 1p-LOH nor N-myc amplification could be detected. This indicates that neuroblastoma in older children is a biologically more heterogenous disorder in which genetic alterations other than deletions of chromosome 1p and amplification of N-myc also may contribute to tumorigenesis.
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PMID:Deletion of chromosome 1p loci and microsatellite instability in neuroblastomas analyzed with short-tandem repeat polymorphisms. 758 54

Expression of the RCK gene, which is a target gene on 11q23 of the t(11;14) (q23;q32) translocation in the B-cell lymphoma cell line RC-K8, was studied by Northern and Western blot analyses. The RCK gene product is a member of the D-E-A-D box protein/RNA helicase family. With the use of Northern blot analysis, a 7.5-kb transcript of the RCK gene was shown to be expressed ubiquitously in human and mouse tissues. Polyclonal antibodies against the RCK gene product were raised, and the RCK gene expression pattern was examined in human and mouse tissues. Two different polyclonal anti-rck antibodies detected a specific 54-kilodalton product named rck/p54 in the majority of human and mouse tissues tested by Western blot analysis. However, rck/p54 was shown to be very low in the human brain and was not detectable in lumbar muscle and lung tissues, although RCK mRNA is abundantly present in these tissues. It is of interest that malignant transformed human cells arising from tissues with low or no expression of rck/p54, such as neuroblastoma, glioblastoma, rhabdomyosarcoma, and lung cancer cell lines, produced a moderate amount of rck/p54 protein, suggesting that rck/p54 plays a role in tumorigenesis. In addition, the rck/p54 protein was localized to cytoplasm by immunostaining with the use of laser microscopy and by subcellular fractionation.
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PMID:The rck/p54 candidate proto-oncogene product is a 54-kilodalton D-E-A-D box protein differentially expressed in human and mouse tissues. 761 84

Bcl-2 protooncogene, originally discovered at the chromosomal breakpoint of the t(14;18) in follicular lymphoma, is known to regulate the process of programmed cell death or apoptosis. The inhibition of apoptosis is thought to be one of the mechanisms involved in the development of tumors. To investigate the possible association of bcl-2 protooncogene with the tumorigenesis of neuroblastomas, the authors examined bcl-2 expression by immunohistochemistry in 49 neuroblastomas and 7 ganglioneuromas. The distribution of apoptotic cells was also examined by the TUNEL method (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Bcl-2 oncoprotein was detected in the cytoplasm in 40 of 49 neuroblastomas (81.6%). There was no correlation between bcl-2 oncoprotein expression and the clinical features of neuroblastoma. The incidence of bcl-2-positive tumors in ganglioneuroma was significantly lower than that in neuroblastoma (28.6%) (P < .01). TUNEL stained the nuclei of tumor cells in 11 of 34 (32.4%) neuroblastomas. TUNEL-positive cells tended to be located around calcifications in neuroblastomas in patients less than 1 year old. Examination of serial sections showed that apoptotic cells were distributed in the area where bcl-2 oncoprotein was not expressed. What we have observed indicates that apoptosis of neuroblastoma cells may be regulated by bcl-2 expression. Our observations suggest that the survival of neuroblastoma cells might be promoted by bcl-2 expression and that bcl-2 might be associated with the tumorigenesis of neuroblastomas.
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PMID:Bcl-2 oncoprotein expression and apoptosis in neuroblastoma. 766 11

Cytogenetic analyses and molecular deletion studies of human neuroblastomas have indicated the chromosomal bands 1p36.1-1p36.2 as a location of genetic information which may be involved in tumorigenesis. To define this putative neuroblastoma locus in more detail we have analysed cell lines with alterations of distal 1p. Here we show, by fluorescence in situ hybridization (FISH), that cell line NGP has a reciprocal 1;15 translocation. Loci D1S214/D1S96 could be shown to map telomeric/distal, D1S228 centromeric/proximal to the break. We have identified yeast artificial chromosomes (YACs) that cover the break and map to D1S160 and D1S244. This chromosomal position is within the smallest region of overlap (SRO) found in neuroblastoma tumors (Weith et al., 1989; Caron et al., 1993; Schleiermacher et al., 1994) and within the region of a constitutional interstitial deletion of a neuroblastoma patient (Biegel et al., 1993). Mapping studies with FISH revealed that the translocation is associated with duplication of DNA. It appears, as if the subchromosomal region we describe here is a good candidate for harboring the postulated neuroblastoma suppressor-gene.
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PMID:A reciprocal translocation (1;15) (36.2;q24) in a neuroblastoma cell line is accompanied by DNA duplication and may signal the site of a putative tumor suppressor-gene. 770 Jun 34

Neuroblastoma (NB), a tumor arising from the sympathetic nervous system, is one of the most common malignancies in childhood. Several recent reports on the p53 genotype found virtually exclusive wild-type status in primary tumors, and it was postulated that p53 plays no role in the development of NB. Here, however, we report that the vast majority of undifferentiated NBs exhibit abnormal cytoplasmic sequestration of wild-type p53. This inability of p53 to translocate to the nucleus presumably prevents the protein from functioning as a suppressor. Thirty of 31 cases (96%) of undifferentiated NB showed elevated levels of wild-type p53 in the cytoplasm of all tumor cells concomittant with a lack of nuclear staining. p53 immunoprecipitation from tumor tissues showed a 4.5- to 8-fold increase over normal protein levels. All of 10 tumors analyzed harbored wild-type p53 by direct sequencing of full-length cDNA and Southern blot. In addition, no MDM-2 gene amplification was seen in all 11 tumors analyzed. In contrast, no p53 abnormality was detected in 14 differentiated ganglioneuroblastomas and 1 benign ganglioneuroma. We conclude that loss of p53 function seems to play a major role in the tumorigenesis of undifferentiated NB. This tumor might abrogate the transactivating function of p53 by inhibiting its access to the nucleus, rather than by gene mutation. Importantly, our results suggest that (i) this could be a general mechanism for p53 inactivation not limited to breast cancer (where we first described it) and that (ii) it is found in a tumor previously not thought to be affected by p53 alteration.
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PMID:Wild-type p53 protein undergoes cytoplasmic sequestration in undifferentiated neuroblastomas but not in differentiated tumors. 775 19

Malignancies of childhood include a well-defined spectrum of hematolymphoid, organ specific (adrenal, kidney, liver), soft tissue, bone, and nervous system (central and peripheral) neoplasms with variable biology. Small round cell neoplasms, a subset of childhood malignancies, are histologically similar but differ markedly in their histogenesis, therapy, and prognosis. Traditionally, clinical information and light microscopy, with the aid of histochemistry and ultrastructural evaluation, establish a diagnosis or at least narrow the differential diagnosis. Additionally, immunohistology, cytogenetics, and molecular studies have become important in diagnosis and in defining phenotype/genotype, patient treatment modalities, and prognosis in specific cases. The 11;22 chromosomal translocation typifies Ewing's sarcoma, primitive neuroectodermal tumor, and Askin's tumor, as does the resultant chimeric transcript, while expression and amplification of N-myc oncogene are predictive of the prognosis in neuroblastoma. Furthermore, studies of genes and gene products are elucidating mechanisms of oncogenesis and tumor progression.
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PMID:Immunohistology, cytogenetics, and molecular studies of small round cell tumors of childhood. A review. 776 71

A monoclonal antibody 6DS1 against a human glioblastoma multiforme cell line U-87MG recognizes a tumor-specific, cell surface antigen of human glioblastoma cell lines. Partial cross-reactivity is observed with two human neuroblastoma cell lines, SK-N-SH and SK-N-MC, with little or no reactivity towards a rat glioma cell line C6 or normal human adult and fetal brain tissues. The antibody recognizes an antigen of molecular mass 38 kDa as inferred from Western blot analysis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoprecipitate. The monoclonal antibody 6DS1 inhibits both the attachment to substratum and growth of U-87MG cells. It strongly cross-reacts with xenotransplants of U-87MG cells and inhibits tumorigenesis (subcutaneous implants of U-87MG cells) in nude mice.
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PMID:Monoclonal antibody against human glioblastoma multiforme (U-87MG) immunoprecipitates a protein of molecular mass 38 kDa and inhibits tumor growth in nude mice. 782 86

Although pediatric solid tumors are cytogenetically less well characterized than childhood leukemias, an understanding of the role of chromosomal changes in the development of these neoplasms is emerging. The major clinical importance of chromosome analysis today is diagnostic. Especially in small cell round cell tumors of childhood, the unique karyotypic patterns that characterize some of the differential diagnostic entities make it possible to determine with a high degree of certainty which type of cancer the child has. Molecular studies have revealed that almost all retinoblastomas show homozygous loss of function of the RB1 gene in 13q14. At the cytogenetic level, however, aberrations of 13q are seen in less than 25% of retinoblastomas; instead, the presumably progression-related i(6p) and aberrations leading to gain of 1q predominate, each being present in one-third of the tumors. Twenty percent of cytogenetically aberrant Wilms' tumors show structural rearrangements, often deletions, of 11p13 and 11p15, where the WT1 and WT2 genes map. Other frequent changes are trisomy 12 and duplication of 1q. The most common (80%) cytogenetic abnormality in neuroblastoma is loss of distal 1p, a chromosome segment thought to harbor at least two tumor-suppressor genes of importance in tumorigenesis. Double minute chromosomes or homogeneously staining regions are present in one-third of all neuroblastomas and are associated with MYCN amplification. Loss of 1p material or MYCN amplification predicts a poor outcome. The most common (30%) chromosomal aberration in primitive neuroectodermal tumors of the central nervous system is i(17q). The formation of this isochromosome may help inactivate a tumor-suppressor gene located distal to the TP53 locus on 17p. No specific chromosome abnormality has been detected in gliomas, but monosomy 22 and rearrangements leading to loss of 1p and gain of 1q are recurrent. Few hepatoblastomas with chromosomal changes have been reported, but several potential primary aberrations have been described, including +2, +20, and duplication 8q. In Ewing's sarcoma, t(11;22)(q24;q12) is the primary aberration, with trisomy 8 and gain of 1q being frequent secondary changes. Fibrosarcomas in children often carry only numeric aberrations, especially trisomy for chromosomes 11, 20, 17, and 8. Most osteosarcomas are cytogenetically complex, and no specific abnormality has been detected; the single most common change is loss of chromosome 13, which is observed in half the tumors. In contrast, the low-malignancy parosteal osteosarcomas often display supernumerary ring chromosomes as the sole karyotypic deviation. The cytogenetic profiles of rhabdomyosarcomas differ among the various morphologic subtypes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytogenetic analysis in the examination of solid tumors in children. 794 9


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