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)

DDX1, a gene mapping to the 2p24 region, has been observed to be co-amplified with MYCN in neuroblastoma. Co-amplification of the DDX1 gene is a consequence of the short physical distance between the two genes. Recently, it has been found that neuroblastoma cells can show a low increase in MYCN gene copy number, defined as MYCN gain. We studied 13 neuroblastomas with MYCN gain to evaluate the status of the DDX1 gene. We investigated DDX1/MYCN gain by double-colour FISH on interphase nuclei. All cases showed concomitant low extra copy number of DDX1 and MYCN. Heterogeneous distribution of nuclei displaying DDX1/MYCN gain was observed in almost all tumours, suggesting a clonal evolution of cells with DDX1/MYCN gain. This is the first report that shows DDX1 co-gained with MYCN in neuroblastoma and indicates that DDX1 over-representation is closely associated with an increase in MYCN copy number in neuroblastoma cells. Since DDX1 has already been found co-amplified with MYCN, DDX1 gain seems to be a further rearrangement due to the physical proximity of the two genes. Moreover, all patients with DDX1/MYCN gain show a good overall survival but a high frequency of adverse events.
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PMID:Concomitant DDX1 and MYCN gain in neuroblastoma. 1761 Oct 20

In order to investigate the replication timing properties of PCDH11X and PCDH11Y, a pair of protocadherin genes located in the hominid-specific non-pseudoautosomal homologous region Xq21.3/Yp11.2, we conducted a FISH-based comparative study in different human and non-human primate (Gorilla gorilla) cell types. The replication profiles of three genes from different regions of chromosome X (ZFX, XIST and ATRX) were used as terms of reference. Particular emphasis was given to the evaluation of allelic replication asynchrony in relation to the inactivation status of each gene. The human cell types analysed include neuronal cells and ICF syndrome cells, considered to be a model system for the study of X inactivation. PCDH11 appeared to be generally characterized by replication asynchrony in both male and female cells, and no significant differences were observed between human and gorilla, in which this gene lacks X-Y homologous status. However, in differentiated human neuroblastoma and cerebral cortical cells PCDH11X replication profile showed a significant shift towards allelic synchrony. Our data are relevant to the complex relationship between X-inactivation, as a chromosome-wide phenomenon, and asynchrony of replication and expression status of single genes on chromosome X.
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PMID:Replication profile of PCDH11X and PCDH11Y, a gene pair located in the non-pseudoautosomal homologous region Xq21.3/Yp11.2. 1767 42

We aimed to directly align a chromosomal CGH (cCGH) pattern with the gene mapping data by taking advantage of the clustering of the GGCC motif at certain positions in the human genome. The alignment of chromosomal with sequence data was achieved by superimposition of (i) the fluorescence intensity of the sequence specific fluorochrome, Chromomycin A3 (CMA3), (ii) the cCGH fluorescence intensity profile of individual chromosomes and (iii) the GGCC density profile extracted from the Ensembl genome sequence database. The superimposition of these three pieces of information allowed us to precisely localize regions of amplification in the neuroblastoma cell line STA-NB-15. Two prominent cCGH peaks were noted, one at 2p24.3, the position 15.4 mega base (Mb), and the other at 2p23.2, 29.51 Mb. FISH and high resolution array CGH (aCGH) experiments disclosed an amplification of MYCN (16 Mb) and ALK (29.2-29.9 Mb), thus confirming the cCGH data. The combined visualization of sequence information and cCGH data drastically improves the resolution of the method to less than 2 Mb.
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PMID:Sequence based high resolution chromosomal CGH. 1854 18

Somatically acquired chromosomal imbalances are a key feature of neuroblastoma, a heterogeneous pediatric solid tumor. Among these alterations, genomic amplification targeting the MYCN oncogene and observed in about 25-30% of the cases, strongly correlates with advanced stage and poor outcome. In this work, we have used BAC and SNP arrays as well as gene expression arrays to characterize amplifications in neuroblastoma. Eighty-eight distinct BACs defining high-level amplification events were identified in 65 samples, including 43 tumors and 22 cell lines. Although the highest recurrence was observed on chromosome 2, clones on chromosomes 8, 12, 16, and 17 also revealed genomic amplification in several samples. A detailed analysis of the 2p22-2p25 MYCN containing region indicated highly complex patterns in a number of cases. Coamplifications involving MYCN and other regions were explored by FISH in three cell lines. High-resolution arrays then allowed us to further refine the mapping of 25 amplicons in 19 samples, either reducing the size of a single continuous amplicon or increasing the complexity by highlighting multiple noncontiguous regions of amplification. Combined analysis of gene expression profiling and array-CGH data indicated that 12 to 25% of the genes that are targeted by genomic amplification are actually over-expressed in tumor cells, several of them having already been implicated in cancer. Finally, our results suggest that the presence of amplicons localized outside of chromosome 2, in addition to MYCN amplification, may be linked to a particularly severe outcome in neuroblastoma patients.
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PMID:Characterization of amplicons in neuroblastoma: high-resolution mapping using DNA microarrays, relationship with outcome, and identification of overexpressed genes. 1855 63

The recognition that genetic defects identify some pediatric solid tumors and may represent prognostic markers has provided cytologists with an extra tool for dealing with such tumors. Using some entities as archetypes, we discuss the importance of the association of fine needle biopsy and genetics, in the diagnosis, prognosis, and therapy selection of solid pediatric tumors. Immunocytochemistry is important to differentiate neuroblastoma, PNET/Ewing sarcoma, alveolar rhabdomyosarcoma, lymphoma, and desmoplastic small round cell tumor. Despite its usefulness in many cases, it is not conclusive and some of the aforementioned tumors even share the expression of some antibodies. The detection of specific diagnostic translocations will thus provide additional information and allows a precise cytologic diagnosis. Kidney tumors are also frequent in children. Although no genetic abnormalities have been identified so far in nephroblastoma, other kidney tumors, such as mesoblastic nephroma, whose cytology pattern can masquerade nephroblastoma, are also characterized by specific translocations. Kidney tumors in children have also been associated recently with typical genetic alterations such as Xp11.2RCC. Concerning prognosis and therapy selection, neuroblastoma is a sort of paradigm. The identification of MYCN oncogene status as an independent prognostic factor is determinant, not only in the assessment of clinical evolution, but also in the identification of risk groups, and consequently in the appropriate therapy selection. Cytopathologists should be aware of the genetic alterations characterizing pediatric tumors in order to collect extra material to perform cytogenetics, FISH, PCR, and Southern blotting, to achieve the correct identification of such genetic changes.
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PMID:Fine needle biopsy and genetics, two allied weapons in the diagnosis, prognosis, and target therapeutics of solid pediatric tumors. 1867 57

The improvement of the imaging has considerably increased the number of cases of neuoroblastoma, diagnosed in preborn age. The authors present a case of neonatal neuroblastoma diagnosed in prenatal age and managed with a multidisciplinary approach. The authors report the case of R.T., born from a scheduled Caesarean delivery. The echographic morphological prenatal diagnosis showed an abdominal mass of 3x2 cm located on the upper side of the kidney, which was not apparently involved. Postnatal ultrasound evaluations confirmed that diagnosis. The diagnostic programme included nuclear magnetic resonance and a renogramm with metaiodobenzylguanidine. These exams confirmed the presence of a mass, probably due to a neuroblastoma. Due to the increasing of the mass, the patient underwent surgical excision of the neoplastic mass. The histological examination confirmed the diagnosis of neuroblastoma Stage I without medullary involvement. During the operation, a medullary biopsy was performed. The FISH exam did not show the amplification of N-myc or a delection of p36 chromosome. For patients younger than 18 months there is no therapeutic gold standard for the treatment of suprarenal masses of neoplastic origin, and the approach is still controversial. The complete excision of the mass should be taken in consideration in presence of an increasing neoformation, and should not include any chemotherapeutical or radiation therapy for stage I, II, IVs (INSS) or L1, MS (INGRSS) neoformations. In conclusion, the effectiveness of a multidisciplinary approach of neonatal neuroblastoma is higher in the early diagnosis and in an accurate staging of the disease, which is fundamental for the favourable prognosis.
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PMID:[Neonatal neuroblastoma and prenatal diagnosis]. 1946 77

Neuroblastoma (NBL) accounts for 6-10% of neoplastic diseases of childhood. The clinical course of NBL is very variable and depends on the presence of prognostic factors. The aim of the study is retrospective evaluation of occurrence of known prognostic factors and disease markers in patients treated in 1991-2005 in our institution. Sixty of 100 treated patients were included to the study, in whom tumor embedded in paraffin was available. In all patients, who had no genetic evaluation at diagnosis, especially MYCN amplification, FISH study was performed. In analyzed group, 29 patients died, 23 of them from NBL. Disease progression (n = 12) or relapse (n = 19) was observed in 31 patients. In the whole analyzed group, age had statistically significant influence on deaths caused by NBL (p = 0.01) and therapy failures (p = 0.00008). The statistically significant increase of NBL death incidence (p = 0.00001) and therapy failures (p = 0.00004) was found in stage 4 patients in comparison with other stages. Presence of MYCN amplification statistically significant decreases overall survival (OS) (p = 0.01) and disease free survival (DFS) (p = 0.047) for the whole analyzed group. However, presence of MYCN amplification had no statistically significant influence on OS and DFS in patients over 1 year of age. Multiple Cox analysis showed independent statistically significant influence of stage and MYCN amplification on prognosis. Employment of new treatment modalities, with treatment intensity adjusted to the risk group, but also with the specificity adapted to tumor characteristics (cytogenetic and molecular) as well as further development of supportive therapy improvement may lead to improvement of treatment results, especially in high risk group and to reduction of therapy complications and improvement of quality of life in all children with this tumor.
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PMID:[Occurrence and prognostic impact of selected factors in neuroblastoma in children]. 2134 68

The family of PITSLRE kinase genes, located in chromosome 1p36, has recently been associated with neuroblastoma tumorigenesis. In order to evaluate the role of these genes as putative tumor suppressor genes, we have analyzed the integrity of the coding region in primary tumors and its location relative to a neuroblastoma consensus deletion. A subset of aggressive neuroblastoma tumors with allelic loss of different parts of chromosome 1p were investigated. Single-strand conformation polymorphism (SSCP), heteroduplex (HD) and sequencing analysis of tumor DNA did not reveal any significant changes in the coding region. In particular, a primary tumor with an interstitial allelic deletion in 1p36 did not reveal concomitant loss of heterozygosity of the PITSLRE gene region when analyzed with a C/T DNA sequence polymorphism in exon 5 of PITSLRE1. FISH analysis on neuroblastoma cell lines with small interstitial deletions and with a balanced translocation in 1p36 revealed that the PITSLRE gene cluster was localized distal to the neuroblastoma consensus deletion. against an involvement of the PITSLRE genes in neuroblastoma tumorigenesis.
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PMID:Analysis of location and integrity of the human PITSLRE (p58(cdc2L1)) genes in neuroblastoma cell genomes. 2154 74

The paper gives the results of investigating the cultured tissues from patients with breast cancer (BC) and those with neuroblastoma, by applying both the traditional studies and molecular genetic techniques (FISH). The cultures from the patients with neuroblastoma represented as three cell types--N, S, and I. There are certain similarities between the cell composition in the culture medium and the histological structure of the tumor. Mature neoplasms of the ganglioneuroma type contain S-type cells only while intermediate type I cells are a predominant element of immature neuroblastomas. The presence of a considerable number of I cells in the explants appears to suggest a poor prognosis even when the tumor has a comparatively mature structure as a whole. The results of FISH on explant cells presented a means of detecting a broad range of points that are not recorded on histologic specimens--amplification on the metaphase plate, localization of an amplified product, amplification on one chromosome, and double acentric chromosomes. The results of cultivation of BC cells are difficult to systematize although they offer the advantage of performing the FISH reaction. The authors recommend that the tissue culture method should be more extensively used in the day-to-day diagnostic work of pathology laboratories.
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PMID:[New feasibility of using a tissue culture technique in diagnostic oncomorphology in case of neuroblastoma and breast cancer]. 2185 22

Most high-risk neuroblastomas develop resistance to cytostatics and therefore there is a need to develop new drugs. In previous studies, we found that ellipticine induces apoptosis in human neuroblastoma cells. We also investigated whether ellipticine was able to induce resistance in the UKF-NB-4 neuroblastoma line and concluded that it may be possible after long-term treatment with increasing concentrations of ellipticine. The aim of the present study was to investigate the mechanisms responsible for ellipticine resistance. To elucidate the mechanisms involved, we used the ellipticine-resistant subline UKF-NB-4(ELLI) and performed comparative genomic hybridization, multicolor and interphase FISH, expression microarray, real-time RT-PCR, flow cytometry and western blotting analysis of proteins. On the basis of our results, it appears that ellipticine resistance in neuroblastoma is caused by a combination of overexpression of Bcl-2, efflux or degradation of the drug and downregulation of topoisomerases. Other mechanisms, such as upregulation of enzymes involved in oxidative phosphorylation, cellular respiration, V-ATPases, aerobic respiration or spermine synthetase, as well as reduced growth rate, may also be involved. Some changes are expressed at the DNA level, including gains, amplifications or deletions. The present study demonstrates that resistance to ellipticine is caused by a combination of mechanisms.
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PMID:Mechanisms of ellipticine-mediated resistance in UKF-NB-4 neuroblastoma cells. 2204 Feb 16


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