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

The gene for the hereditary disorder neurofibromatosis type 2 (NF2), which predisposes for benign CNS tumors such as vestibular schwannomas and meningiomas, has been assigned to chromosome 22 and recently has been isolated. Mutations in the NF2 gene were found in both sporadic meningiomas and vestibular schwannomas. However, so far only 6 of the 16 exons of the gene have been analyzed. In order to extend the analysis of an involvement of the NF2 gene in the sporadic counterparts of these NF2-related tumors, we have used reverse transcriptase-PCR amplification followed by SSCP and DNA sequence analysis to screen for mutations in the coding region of the NF2 gene. Analysis of the NF2 gene transcript in 53 unrelated patients with meningiomas and vestibular schwannomas revealed mutations in 32% of the sporadic meningiomas (n = 44), in 50% of the sporadic vestibular schwannomas (n = 4), in 100% of the tumors found in NF2 patients (n = 2), and in one of three tumors from multiple-meningioma patients. Of the 18 tumors in which a mutation in the NF2 gene transcript was observed and the copy number of chromosome 22 could be established, 14 also showed loss of (parts of) chromosome 22. This suggests that in sporadic meningiomas and NF2-associated tumors the NF2 gene functions as a recessive tumor-suppressor gene. The mutations detected resulted mostly in frameshifts, predicting truncations starting within the N-terminal half of the putative protein.
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PMID:Frequent NF2 gene transcript mutations in sporadic meningiomas and vestibular schwannomas. 791 Oct 2

Meningiomas frequently show mutational inactivation of the neurofibromatosis type 2 tumor suppressor gene (NF2 gene). In a previous study, mutations were preferentially observed in the fibroblastic and transitional subtypes (75%), whereas the meningothelial variant was significantly less affected (25%). To study a potential role of the NF2 gene on the transcriptional level, we have analyzed NF2 transcripts in 67 meningiomas of different subtypes. A competitive reverse transcriptase-PCR assay with an external NF2 gene standard was used for quantitative mRNA analysis. Fibroblastic and transitional meningiomas exhibited significantly lower levels of NF2 mRNA compared with meningothelial variants (p = 0.001, unpaired t test). These data support the concept of a distinct molecular pathway in the formation of meningothelial meningiomas independent from the NF2 gene or its gene product merlin/schwannomin. In addition, in these tumors, NF2 expression was reduced by a factor of 10 (p < 0.001, unpaired t test) in those meningiomas with NF2 gene mutations suggesting decreased stability or impaired transcription of mutated NF2 mRNA. In conclusion, our data provide further evidence for molecular differences between subtypes of meningiomas and support an NF2-independent pathogenesis of meningothelial meningiomas.
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PMID:Quantitative analysis of neurofibromatosis type 2 gene transcripts in meningiomas supports the concept of distinct molecular variants. 942 97

Mutation detection in the neurofibromatosis type 2 (NF2) gene is challenging because when combining mutation detection methods such as single-strand conformational polymorphism and heteroduplex analysis, denaturing gradient gel electrophoresis, and direct sequencing of aberrant polymerase chain reaction (PCR) fragments only 30 to 60% of the constitutional mutations are detected. Because large deletions and complete chromosome rearrangements are also described methods such as microarray-comparative genomic hybridization and fluorescence in situ hybridization are also used. The one type of mutation often missed corresponds to deletions encompassing one or few exons. To detect this type we have developed a swift and reliable method. We perform a gene dosage analysis with two fluorescent multiplex PCR assays that amplify 15 of the 17 NF2 exons. The labeled PCR products are quantified and gene dose is calculated with respect to controls. We tested the reliability of this method with DNA from eight NF2 patients with known heterozygous NF2 deletions, eight controls and four unknown NF2 patients. In all of the patients with known heterozygous deletions we found in several exons a reduction of gene dosage to 50 to 69%. In one NF2 patient with previously unknown mutation and a severe phenotype we found the gene dosage of two exons reduced by 50% indicating a deletion of these two exons on one allele. This finding was validated by reverse transcriptase-PCR on fibroblast and schwannoma cell cultures of this patient and cDNA sequencing. Our gene dosage assay will detect deletions of one or more exons as well as gross deletions of the whole coding region of the gene. It can complement the existing screening methods because it is faster and easier.
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PMID:Sensitive detection of deletions of one or more exons in the neurofibromatosis type 2 (NF2) gene by multiplexed gene dosage polymerase chain reaction. 1568 80