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  • 1
    ISSN: 1573-7373
    Keywords: p53 gene ; astrocytoma ; loss of heterozygosity ; mutation ; frozen tissue section ; second malignant neoplasm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The polymorphism of amino acid residue 72 on the humanp53 tumor-suppressor gene is a useful marker for detecting intragenic loss of heterozygosity (LOH). We examined the LOH of thep53 gene in human malignant astrocytomas by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using DNA extracted from frozen tissue sections under histologic examination. Eleven of 16 informative cases (69%) of the malignant astrocytomas were found to have LOH in thep53 gene. Sequential frozen sections were analyzed by immunohistochemistry using anti-p53 antibody PAb1801 to detect overexpression of the p53 protein, which is presumably altered if it is detectable. Ten of the 11 cases that had LOH of thep53 gene overexpressed the p53 protein. Moreover, 4 of the 11 patients with LOH of thep53 gene developed a second neoplasm in addition to an astrocytoma, possibly indicating genetic instability in these patients. These data suggest that alterations of thep53 gene may play an important role in the genesis of malignant astrocytoma. The combination of the PCR-RFLP method and immunohistochemical analysis using frozen tissue sections is a practical diagnostic tool for examination of human malignancies, including astrocytomas.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neuro-oncology 21 (1994), S. 151-157 
    ISSN: 1573-7373
    Keywords: clonal analysis ; astrocytoma ; glioma ; brain tumor ; X-chromosome inactivation ; restriction fragment length polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clonal analysis of many human cancers have generally confirmed that they are monoclonal. Although astrocytic neoplasms are the most frequently occuring primary tumors in the central nervous system, their clonal composition has not been systematically studied. In this report, the clonal composition of 22 human astrocytomas of all histological grades (2 well-differentiated astrocytomas, 3 anaplastic astrocytomas and 17 glioblastoma multiforme) was determined by analysis of the pattern of X-chromosome inactivation. Leukocyte and non-tumor brain DNA were used as controls. In addition, specimens from different parts of four glioblastoma multiforme were analyzed to determine whether remote areas of the same tumor had the same clonal composition. Eighteen of nineteen informative astrocytomas had a monoclonal pattern of X-chromosome inactivation; one glioblastoma multiforme had loss of heterozygosity on the X chromosome. Specimens from different areas of the same tumor all had identical patterns of X-chromosome inactivation. Leukocytes and non-tumor brain used as controls uniformly had a polyclonal pattern of X-chromosome inactivation. Furthermore, loss of heterozygosity for chromosomes 10 or 17 p loci was found in 64% (9/14) of informative specimens and identical allelic patterns were observed in specimens from different areas of the same tumor. Our results demonstrate that human astrocytomas from low to high-grade are characterized by monoclonal cell populations. The presence of monoclonality in even low-grade neoplasms suggests that in astrocytic tumors the establishment of monoclonality occurs quite early. Also, the finding of a monoclonal pattern in intermediate- and high-grade astrocytomas further supports the hypothesis that clonal expansion underlies astrocytic tumor progression.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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