Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Damselfish neurofibromatosis (DNF) is a naturally occurring, neoplastic disease affecting bicolor damselfish (Pomacentrus partitus) living on coral reefs in southern Florida, USA. The disease consists of multiple neurofibromas, neurofibrosarcomas and chromatophoromas and has been proposed as an animal model for neurofibromatosis type 1 in humans. DNF is transmissible by injection of crude tumour homogenates, cell-free filtrates of homogenates or cells from tumour cell lines. An analysis of tumorigenic cell lines derived from fish with spontaneous or experimentally induced DNF revealed virus particles budding from cells and present in conditioned media. The 90-110 nm particles resembled type C retroviruses. This virus exhibited a buoyant density of 1.14-1.17 g/cm2 in sucrose, at least six virus proteins of 15 to 80 kDa and reverse transcriptase (RT) activity. RT activity was maximized with a poly(rC).oligo(dG) template.primer combination and Mn2+ at a concentration of 0.5-1.0 mM. The optimum temperature for RT was determined to be 20 degrees C, a finding consistent with the ambient temperatures encountered by this species. This retrovirus, tentatively named damselfish neurofibromatosis virus (DNFV) may be the aetiological agent of DNF. Whether DNFV or another, as yet unidentified, virus is the cause of DNF, this agent may be unique in virus oncogenesis; neoplastic transformation of the cell types involved in DNF, Schwann cells and chromatophores, has not been documented in any other transmissible tumour.
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PMID:A retrovirus isolated from cell lines derived from neurofibromas in bicolor damselfish (Pomacentrus partitus). 868 5

To verify the absence of the synovial sarcoma translocation t(X;18) (SYT-SSX) in malignant peripheral nerve sheath tumors, 34 tumor samples from 25 neurofibromatosis type 1 patients were examined in two independent laboratories (Bordeaux, France, and Lausanne, Switzerland) using reverse transcriptase polymerase chain reaction (RT-PCR)-based techniques. RNA was extracted from paraffin blocks using standard methods, reverse transcribed, and conventional (in one laboratory) versus real-time (in the other laboratory) PCR performed. Twenty-seven tumor samples from 19 patients were negative for the t(X;18) in both laboratories; six additional tumors that were t(X;18)-negative in one laboratory gave noninterpretable results in the other, due to lack of internal positive controls; one case was noninterpretable in both places. In conclusion, malignant peripheral nerve sheath tumors in neurofibromatosis type 1 patients do not bear the synovial sarcoma t(X;18) (SYT-SSX). Laboratories that use PCR-based techniques for diagnostic purposes would benefit from quality assurance programs.
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PMID:Malignant peripheral nerve sheath tumors are t(X;18)-negative sarcomas. Molecular analysis of 25 cases occurring in neurofibromatosis type 1 patients, using two different RT-PCR-based methods of detection. 1206 70

Neurofibromatosis type 1 (NF1) is a common genetic disease caused by haploinsufficiency of the NF1 tumor-suppressor gene. Different pathogenetic mechanisms have been identified, with the majority (95%) causing intragenic lesions. Single or multiexon NF1 copy number changes occur in about 2% of patients, but little is known about the molecular mechanisms behind these intragenic deletions. We report here on the molecular characterization of a novel NF1 multiexonic deletion. The application of a multidisciplinary approach including multiplex ligation-dependent probe amplification, allelic segregation analysis, and fluorescent in situ hybridization allowed us to map the breakpoints in IVS27b and IVS48. Furthermore, the breakpoint junction was characterized by sequencing. Using bioinformatic analysis, we identified some recombinogenic motifs in close proximity to the centromeric and telomeric breakpoints and predicted the presence of a mutated messenger ribonucleic acid, which was deleted between exons 28 and 48 and encodes a neurofibromin that lacks some domains essential for its function. Through reverse transcriptase-polymerase chain reaction, the expression of the mutated allele was verified, showing the junction between exons 27b and 49 and, as expected, was not subjected to nonsense-mediated decay. Multiexonic deletions represent 2% of NF1 mutations, and until now, the breakpoint has been identified in only a few cases. The fine characterization of multiexonic deletions broadens the mutational repertoire of the NF1 gene, allowing for the identification of different pathogenetic mechanisms causing NF1.
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PMID:Breakpoint characterization of a novel NF1 multiexonic deletion: a case showing expression of the mutated allele. 1819

Recent studies found that serum microRNAs (miRNAs) could serve as stable and noninvasive biomarkers for disease diagnosis. We used genome-wide serum miRNA expression analysis to investigate the role of serum miRNAs in distinguishing malignant peripheral nerve sheath tumor (MPNST) patients with and without neurofibromatosis type 1 (NF1) from NF1 patients. A total of 100 patients with NF1, 93 sporadic MPNST patients, and 71 NF1 MPNST patients were enrolled in this two-stage, case-control study. Solexa sequencing was used to screen for miRNAs that expressed differentially in three pooled serum samples from 10 NF1 patients, 10 sporadic MPNST patients, and 10 NF1 MPNST patients. The detected serum miRNAs then were validated in 90 patients with NF1, 83 patients with sporadic MPNST, and 61 NF1 MPNST patients by individual quantitative reverse transcriptase polymerase chain reaction assays. Eight serum miRNAs altered more than fivefold by Solexa sequencing between MPNST patients (with and without NF1) and NF1 patients. MiR-801 and miR-214 increased both in sporadic MPNST patients and NF1 MPNST patients when compared with NF1 patients. The sensitivity and the specificity of sporadic MPNST detection by the two-miRNA signature were 0.747 and 0.856, respectively. MiR-24 was only significantly up-regulated in NF1 MPNST patients. The combination of the three miRNAs (MiR-801, miR-214, and miR-24) could distinguish NF1 MPNST patients from NF1 patients with a sensitivity of 0.820 and a specificity of 0.844. The serum-based miRNA expression profiles could serve as novel noninvasive biomarkers in sporadic MPNST and NF1 MPNST detection.
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PMID:Identification of serum microRNAs in genome-wide serum microRNA expression profiles as novel noninvasive biomarkers for malignant peripheral nerve sheath tumor diagnosis. 2348 52