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  • 1
    ISSN: 1573-7373
    Keywords: RLGS ; gel electrophoresis ; genetic subtypes ; glioblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The 16 primary gliomas were examined for changes in genomic DNA using arecently developed 2-dimensional gel electrophoresis method calledrestriction landmark genomic scanning (RLGS). This approach allows detectionof DNA amplification, deletion, methylation and potentially other geneticrearrangements represented as decreases and increases in spot/fragmentintensity on an autoradiogram. Approximately 2,000 landmark sites in tumorDNA were compared with those of DNA isolated from normal brain tissues.Seven spots showing intensified signal were consistently detected in atleast 50% of tumors, implying activation of corresponding DNAsequences, and 8 additional spots having reduced signal were observed, againin more than 50% of all tumors, suggesting inactivation by the lossof 1 allele or homozygous deletion. Decreased signal may also infer relativeCpG island methylation state. Of those spots consistently identified intumors, 2 amplified and 4 reduced spots were found to be characteristic oflow- and high-grade tumors, while the remaining 5 amplified and 4 reducedspots were associated with high-grade gliomas only, suggesting a link ofspecific mutations to degree of malignancy. A separate subset ofglioblastomas evaluated, however, showed no alterations in these ’hot spots‘which were detected in even low grade astrocytomas. The results demonstratethe genetic heterogeneity of glioblastoma and implicate the progression ofneoplasia via differing genetic pathways.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of human genetics 44 (1999), S. 354-355 
    ISSN: 1435-232X
    Keywords: Key wordshSNF5/INI1 gene ; Single nucleotide polymorphism ; Malignant rhabdoid tumor ; Chromosome 22q11.2 ; Tumor suppressor gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We found two single nucleotide polymorphisms at the hSNF5/INI1 gene located on 22q11.2, encoding a member of the chromatin-remodelling SWI/SNF multiprotein complexes. A guanine/adenine polymorphism at codon 299 in exon 7, and another guanine/adenine polymorphism at 39 bp upstream of exon 9 were identified. As the gene was recently identified as a tumor suppressor gene for malignant rhabdoid tumor, this polymorphism may be useful for the genetic study of susceptibility for human malignancies of various tissue origins.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1861-387X
    Keywords: Recurrent astrocytic tumors ; Two-dimensional gel electrophoresis ; Genome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The genetic mechanisms associated with recurrence of advanced astrocytic tumors are poorly understood. We therefore analyzed 24 biopsy specimens from 12 patients with a recurrent astrocytic tumor by a two-dimensional gel electrophoresis method, termed restriction landmark genomic scanning (RLGS). Four spot changes were commonly present in the primary astrocytomas, indicating that the corresponding gene alterations were early events in the development of this tumor type. Altered spots were more frequent and of different distribution in recurrent tumors than in the primary astrocytomas. In particular, specifically increased intensity for spots on chromosomes 9–12 and 18 and reduced intensity for spots on 9–12 and 18 were observed in the secondary tumors, suggesting a relation with recurrence. The same spot changes observed in primary tumors were also found in the respective secondary lesions but with strikingly different densities in some cases, suggesting increased genetic instability. The altered segments provide important candidate regions for the search for genes involved in events leading to progression and more malignant recurrent tumors.
    Type of Medium: Electronic Resource
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