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)

Dicer is a ribonuclease playing a key role in the biogenesis of microRNAs and small interfering RNAs. Here we report the identification of a novel splice variant of human dicer gene, the first one bearing a modified coding sequence. It encodes a truncated protein, t-Dicer that lacks the dsRNA-binding domain and is defective in one of the two RNase III catalytic centers. The splice variant was found in neuroblastoma cells and in cells induced to neuronal differentiation, whereas it was not detectable in other cell lines or in normal tissues. Interestingly, it occurred in primary neuroblastic tumors, mainly in stroma poor neuroblastomas.
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PMID:A novel splice variant of the human dicer gene is expressed in neuroblastoma cells. 2061 7

Dicer is central to small RNA silencing pathways, thus playing an important role in physiological and pathological states. Recently, a number of mutations in dicer gene have been identified in diverse types of cancer, implicating Dicer in oncogenic cooperation. Here we report on the properties of a rare splice variant of the human dicer gene, occurring in neuroblastoma cells, and not detectable in normal tissues. Due to the skipping of one exon, the alternatively spliced transcript encodes a putative truncated protein, t-Dicer, lacking the dsRNA-binding domain and bearing altered one of the two RNase III catalytic centers. The ability of the exon-depleted t-dicer transcript to be translated in vitro was first investigated by the expression of flagged t-Dicer in human cells. We found that t-dicer transcript could be translated in vitro, albeit not as efficiently as full-length dicer transcript. Then, the possible enzymatic activity of t-Dicer was analyzed by an in vitro dicing assay able to distinguish the enzymatic activity of the individual RNase III domains. We showed that t-Dicer preserved partial dicing activity. Overall, the results indicate that t-dicer transcript could produce a protein still able to bind the substrate and to cleave only one of the two pre-miRNA strands. Given the increasing number of mutations reported for dicer gene in tumours, our experimental approach could be useful to characterize the activity of these mutants, which may dictate changes in selected classes of small RNAs and/or lead to their aberrant maturation.
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PMID:Characterization of a naturally occurring truncated Dicer. 2591 Nov 88

Pleuropulmonary blastoma (PPB), the most common primary malignant neoplasm of the lung in childhood, occurs in the same early age group (0-6 years) as the other more common solid tumors such as neuroblastoma and Wilms tumor. The tumor begins as a cystic lung lesion with the potential over a period of 3-5 years to progress to a high grade multipatterned primitive sarcoma in the absence of a malignant epithelial component. Several years after its initial description as a unique clinicopathologic entity, this and other tumors appeared to have a familial predilection which was later confirmed with the discovery of a heterozygous germline mutation in DICER1 whose protein is a member of ribonuclease III family of enzymes. It is estimated that 75%-80% of children with a PPB have the germline mutation. The other notable finding from our studies is the identification of a family of extrapulmonary neoplasms, including cystic nephroma and Sertoli-Leydig cell tumor of the ovary as two examples, also with DICER1 mutations.
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PMID:Pleuropulmonary Blastoma: More Than a Lung Neoplasm of Childhood. 3152 43