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

To investigate the mechanism behind JC virus (JCV) cell specificity we performed electrophoretic mobility shift assays (EMSA) using probes derived from the JCV transcriptional control region (JCV-TCR). Using nuclear extracts from the JCV-susceptible neuroblastoma cell line IMR-32, EMSA revealed a 670 kDa JCV-TCR-binding protein complex designated as #3-bp. This complex could not be detected in nuclear extracts from non-susceptible cell lines. Using column chromatographic purifi-cation and microsequencing, we identified cleavage stimulation factor (CstF) as a component of #3-bp. However, as CstF is present in many cell types, we speculated that the IMR-32-specific component(s) of #3-bp bind CstF. We performed a yeast two-hybrid assay using CstF-77 as the bait against a HeLa cDNA-subtracted IMR-32 cDNA library. This analysis detected binding between CstF-77 and the RNA helicase DDX1. Subsequently, biotinylated DNA affinity precipitation and chromatin immunoprecipitation assays also confirmed that DDX1 binds specifically to JCV-TCR. Our findings indicate that an association between DDX1 and the JCV-TCR may play a significant role in JCV infection in IMR-32 cells.
 ...
PMID:Identification of DDX1 as a JC virus transcriptional control region-binding protein. 1738 53

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.
 ...
PMID:Concomitant DDX1 and MYCN gain in neuroblastoma. 1761 Oct 20

DEAD box proteins are a family of putative RNA helicases associated with all aspects of cellular metabolism involving the modification of RNA secondary structure. DDX1 is a member of the DEAD box protein family that is overexpressed in a subset of retinoblastoma and neuroblastoma cell lines and tumors. DDX1 is found primarily in the nucleus, where it forms two to four large aggregates called DDX1 bodies. Here, we report a rapid redistribution of DDX1 in cells exposed to ionizing radiation, resulting in the formation of numerous foci that colocalize with gamma-H2AX and phosphorylated ATM foci at sites of DNA double-strand breaks (DSBs). The formation of DDX1 ionizing-radiation-induced foci (IRIF) is dependent on ATM, which was shown to phosphorylate DDX1 both in vitro and in vivo. The treatment of cells with RNase H prevented the formation of DDX1 IRIF, suggesting that DDX1 is recruited to sites of DNA damage containing RNA-DNA structures. We have shown that DDX1 has RNase activity toward single-stranded RNA, as well as ADP-dependent RNA-DNA- and RNA-RNA-unwinding activities. We propose that DDX1 plays an RNA clearance role at DSB sites, thereby facilitating the template-guided repair of transcriptionally active regions of the genome.
 ...
PMID:A role for DEAD box 1 at DNA double-strand breaks. 1871 Sep 41

Somatic and germline mutations of the anaplastic lymphoma kinase (ALK) gene were recently described in neuroblastoma (NB). In this study, we investigated the association of ALK copy number alterations with copy number status 2p24.1 amplicon harboring DEAD box polypeptide 1 (DDX1), MYCN and neuroblastoma-amplified (NAG) genes in 90 primary tumors of sporadic NB cases by multiplex ligation-dependent probe amplification (MLPA). We also performed mutation analysis of ALK gene by directly sequencing the exons 20-28 which cover the region that encodes juxtamembrane and kinase domains. A total of 39 (43.3%) NB cases revealed copy numbers alterations of ALK gene. There was highly significant association of ALK copy number gains with gains of one or more of the genes at 2p24.1 (DDX1, MYCN or NAG) in MYCN unamplified tumors (P<0.000). In addition, 15 of 17 MYCN amplified cases (88.2%) had aberrant ALK status. Solitary gain of ALK with normal copy number status of all other genes was observed only in one case. DNA sequencing of exons 20-28 of ALK revealed two different nucleotide changes in three cases leading to amino acid substitutions of F1245V and R1275Q in tyrosine kinase domain. In conclusion, the frequency of ALK mutations in NB is low and solitary copy number change of it is rarely observed.
 ...
PMID:Copy number status and mutation analyses of anaplastic lymphoma kinase (ALK) gene in 90 sporadic neuroblastoma tumors. 2208 94

This report concerns a 3-year-old girl with prenatal bilateral nephroblastomatosis and a family history of nephroblastoma. This girl had a chromosome 8 pericentric inversion inherited from her father. This inversion was observed in healthy individuals of the family and was absent in other individuals suffering from embryonic kidney tumor. We then supposed that another genetic anomaly predisposed her to tumorogenesis. Additional cryptic imbalances are reported in cases of apparently balanced chromosomal rearrangements with an abnormal phenotype. Array-CGH analysis showed a 569 kb duplication at 2p24.3 including the DDX1 and MYCN genes. This duplication was inherited from the patient's father who also had a nephroblastoma. A link between germline MYCN duplication and the occurrence of other embryonic cancers such as neuroblastoma has already been described. We supposed that germline DDX1-MYCN duplication could also be involved in the apparition of nephroblastomas.
 ...
PMID:Involvement of germline DDX1-MYCN duplication in inherited nephroblastoma. 2416 95


<< Previous 1 2