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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the loss of tumor suppressor genes and the activation of oncogenes have been established as two of the fundamental mechanisms of tumorigenesis in human cancer, little is known about the possible interactions between these two mechanisms. Loss of genetic material on chromosome 10 and amplification of the epidermal growth factor receptor (EGFR) gene are the most frequently reported genetic abnormalities in glioblastoma multiforme. In order to examine a possible correlation between these two genetic aberrations, the authors studied 106 gliomas (58 glioblastomas, 14 anaplastic astrocytomas, five astrocytomas, nine pilocytic astrocytomas, seven mixed gliomas, six oligodendrogliomas, two ependymomas, one subependymoma, one subependymal giant-cell astrocytoma, and three gangliogliomas) with Southern blot analysis for loss of heterozygosity on both arms of chromosome 10 and for amplification of the EGFR gene. Both the loss of genetic material on chromosome 10 and EGFR gene amplification were restricted to the glioblastomas. Of the 58 glioblastoma patients, 72% showed loss of chromosome 10 and 38% showed EGFR gene amplification. The remaining 28% had neither loss of chromosome 10 nor EGFR gene amplification. Without exception, the glioblastomas that exhibited EGFR gene amplification had also lost genetic material on chromosome 10 (p less than 0.001). This invariable association suggests a relationship between the two genetic events. Moreover, the presence of 15 cases of glioblastoma with loss of chromosome 10 but without EGFR gene amplification may further imply that the loss of a tumor suppressor gene (or genes) on chromosome 10 precedes EGFR gene amplification in glioblastoma tumorigenesis.
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PMID:Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. 132 Jun 66

Cytogenic and molecular genetic analyses of the major histological subtypes of nervous system tumors, gliomas, meningiomas, and neurinomas, have provided interesting information on the mechanisms responsible for or contributing to their origin and development. Regarding malignant gliomas, a complex pattern of chromosomal involvement has been documented at the cytogenetic level: gains of chromosome 7 and losses of chromosome 10, 9p, 17p, and 22; further molecular characterization of these abnormalities has shown that mutational alterations of the p53 gene, together with the loss of alleles at 17p, seem to be the earliest abnormalities occurring during the genesis and progression of these neoplasms. The losses of regions on chromosomes 22 and 13 might also be relatively early events, perhaps characterizing subgroups of low grade gliomas. The mutations of the p53 gene in low grade tumors leads to a selective advantage in vivo and seems to be a critical step in the transformation from low grade to high grade gliomas. The loss of sequences on chromosome 10 and the deletions of 9p (that is loss of tumor suppressor genes on these locations), and epidermal growth factor receptor gene amplification, have been proposed as sequential abnormalities participating in glioblastoma tumorigenesis. The available data on meningiomas and neurinomas show that loss of regions on chromosome 22 is the main characteristic feature. Thus, tumor suppressor genes located in this chromosome are non-randomly involved in both neoplasms, and may present as solitary, sporadic tumors or as multiple associated lesions in neurofibromatosis type 2 (NF-2). The molecular analysis of a large series of meningiomas to determine the common chromosome 22 region lost has revealed that a putative meningioma tumor suppressor gene should be located at the distal 22q12.3-qter region. In parallel, the linkage data on the mapping of the NF-2 gene suggest that the NF-2 and meningioma loci are separate entities. However, some evidence exists on a possible participation of the NF-2 locus in the genesis of some meningiomas. The efforts to identify and isolate the genes involved, as well as their functional analysis, will contribute to a better understanding of the mechanisms of oncogenesis in these neoplasms and will doubtless have a clinical impact in the diagnosis, treatment and prognosis of nervous system tumors in patients.
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PMID:Cytogenetics and molecular genetics of nervous system tumors. 133 85

A number of protooncogenes have been implicated in human tumorigenesis. The ABL oncogene is consistently rearranged and activated as a consequence of the translocation t(9;22) that gives rise to the Philadelphia chromosome in chronic myeloid leukemia and in some cases of acute lymphoblastic leukemia. Here we describe rearrangement of ABL in a different type of malignancy. The glioblastoma cell line A172 lacks germline alleles of ABL. A recombination event, presumably followed by a duplication, has created two ABL alleles in which exon 11 is joined to chromosome 16 sequences. Although the main body of ABL exons was still present, two considerably shortened ABL mRNAs of 3.8 and 2.8 kilobases were detected; the 3.8-kilobase mRNA hybridized exclusively to an exon IB probe. Neither mRNA hybridized to an ABL probe encompassing part of the tyrosine kinase domain. Thus, the cell line A172 is able to survive in the absence of a functional ABL gene product, indicating that the role of ABL is unlikely to be "housekeeping."
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PMID:Rearrangement of the human ABL oncogene in a glioblastoma. 233 39

The present study determined which oncogenes (N-myc, c-myc, v-sis, or v-fos) were amplified and which messenger ribonucleic acids (mRNA's) accumulated in 10 primary human brain tumors of neuroectodermal origin. The tumors included four glioblastomas multiforme, one mixed glioma (astrocytoma grade I and ependymoma), one astrocytoma grade II, one cystic cerebellar astrocytoma, one ependymoma, one ganglioglioma, and one medulloblastoma. The relative amounts of polyadenylated (poly(A)+) RNA's homologous to these genes and their copy number were determined using the RNA and deoxyribonucleic acid blot hybridization techniques. The N-myc and v-sis probes hybridized strongly to the poly(A)+ RNA from the same recurrent glioblastoma with gene amplifications (N-myc 80 copies; v-sis three to four copies). The c-myc probe hybridized strongly to the recurrent medulloblastoma without gene amplification. The amplification or abundant accumulation of mRNA's homologous to their oncogenes may be involved in tumorigenesis or the aggressiveness of these malignant brain tumors of neuroectodermal origin and may be good molecular indicators of an extremely malignant state in these tumors.
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PMID:Proto-oncogene analyses in brain tumors. 254 Dec 27

Allelic combinations at seven loci on human chromosome 17 defined by restriction fragment length polymorphisms were determined in tumor and normal tissues from 35 patients with gliomas. Loss of constitutional heterozygosity at one or more of these loci was observed in 8 of the 24 tumors displaying astrocytic differentiation and in the single primitive neuroectodermal tumor examined. The astrocytomas showing these losses included examples of each adult malignancy grade of the disease, including glioblastoma (malignancy grade IV), and seven of them demonstrated concurrent maintenance of heterozygosity for at least one chromosome 17 locus. Determination of allele dosage together with the genotypic data indicated that the tumor chromosomes 17 were derived by mitotic recombination in 7 of the 9 cases with shared homozygosity of the region 17p11.2-pter in all cases. In contrast, tumors of oligodendrocytic, ependymal, or mixed cellular differentiation did not exhibit loss of alleles at any of the loci examined. These data suggest that the somatic attainment of homozygosity for loci on chromosome 17p is frequently associated with the oncogenesis of central nervous system tumors, particularly those showing solely astrocytic differentiation, and that mitotic recombination mapping is a useful approach towards the subregional localization of a locus whose rearrangement is involved in this disease.
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PMID:Mitotic recombination of chromosome 17 in astrocytomas. 256 39

Loss of constitutional heterozygosity for specific chromosomal loci, when found consistently in a particular tumor type, suggests that a recessive oncogene important in the genesis of that tumor may be present within the involved chromosomal loci. DNA markers that detect restriction fragment length polymorphisms are powerful tools that have been used to detect loss of chromosomal loci in a growing number of human malignancies. The human brain tumor astrocytoma is usually malignant and virtually incurable. Two types of malignant astrocytomas are recognized histopathologically:anaplastic astrocytoma and glioblastoma multiforme. We carried out a restriction fragment length polymorphism analysis of tumors from 15 patients with anaplastic astrocytoma and 20 patients with glioblastoma using polymorphic DNA markers for loci on chromosome 17. Loss of constitutional heterozygosity for loci on chromosome 17 was found in both anaplastic astrocytoma and glioblastoma patients with equal frequency (40% of cases). Our mapping data revealed a region of loss on chromosome 17p between physical loci p11.2 and pter that was common to both patient groups. Taken together with the previously reported finding of loss of heterozygosity for loci on chromosome 10 in glioblastoma, these results indicate that tumorigenesis in the astrocyte lineage may involve recessive oncogenes on two different chromosomes.
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PMID:Loss of heterozygosity for loci on chromosome 17p in human malignant astrocytoma. 257 17

Expression of the c-sis oncogene, the gene encoding the B chain of platelet-derived growth factor (PDGF), may be related to initiation and/or progression of glial cell tumorigenesis by PDGF-mediated autocrine growth stimulation. As the mechanism for activation of expression of the c-sis gene in gliomas is not known, we searched for possible structural alterations of c-sis DNA in these tumors. Genomic Southern blots of DNA from 7 different cultured human glioblastoma cell lines and 15 different solid human brain tumors revealed no significant change in either the gross structure or the copy number of the c-sis gene in tumor cells vs. control cells. Activation of glioma c-sis gene expression is therefore not the result of a gross rearrangement or amplification of the c-sis gene. Expression of c-sis mRNA was detected in all of 12 different solid human brain tumors, 11 of which were of glial cell origin. However, in tissue adjacent to 5 different tumors, approximately the same level of c-sis mRNA was seen.
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PMID:Major structural alterations of the c-sis gene are not observed in a series of tumors of the human central nervous system. 258 29

Human glioblastomas are highly malignant intracranial tumors, some of which demonstrate amplification of the epidermal growth factor-receptor (EGF-R) gene. Overexpression of this gene is seen in the majority of primary tumors; however, the role of the EGF-R gene in glial tumorigenesis is unknown. The authors explored the relationship between EGF-R gene expression and glioblastoma cell growth in vitro and in vivo and found that this level of EGF-R gene expression did not correlate with tumor cell growth either in soft agar or in the nude mouse. This suggests that the EGF-R gene is not involved in effecting direct growth stimulation in glial oncogenesis. Tumorigenesis involves differentiation arrest; therefore, the expression of several proto-oncogenes in neuroectodermal tumors was investigated to evaluate the potential involvement of the EGF-R gene in glial differentiation. A nonoverlapping expression of the N-myc and EGF-R genes was found in neuronal-derived and glial-derived tumors, respectively. This suggests that the EGF-R gene may be involved in differentiation or its arrest in glia.
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PMID:Proto-oncogene abnormalities and their relationship to tumorigenicity in some human glioblastomas. 273 45

The production of platelet-derived growth factor like (PDGF-like) material by glioblastomas may be involved in the conversion of normal cells to tumor cells. In an investigation of this problem, we have examined some of the properties of the platelet-derived growth factor B-chain mRNA (c-sis mRNA) by a sensitive and quantitative RNA-RNA solution hybridization method. In 5 out of 8 human glioblastoma cell lines, c-sis mRNA was present, and in the line with the highest level, there were approximately 4-10 molecules per cell. The half-lives of the c-sis mRNA in two glioblastoma cell lines were 2.6 and 3.4 h, while in human umbilical vein endothelial (HUVE) and bladder carcinoma (T24) cells they were 1.6 and 2.5 h, respectively. Inhibiting protein synthesis produced no significant alteration of the c-sis mRNA half-lives in the glioblastoma or HUVE cells. The A-U-rich sequence at the 3' end of the c-sis mRNA therefore does not appear to affect the mRNA stability in the presence of cycloheximide as it does in other transcripts. The similarity of the c-sis mRNA half-lives in normal and tumor cells suggests that regulation of stability of c-sis mRNA is not a major factor in tumorigenesis in the glioblastoma cell lines examined.
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PMID:Expression and stability of c-sis mRNA in human glioblastoma cells. 305 84

In normal human tissue high concentrations of the neuropeptide head activator are found in the hypothalamus, in the retina, and in the gastro-intestinal tract. Up to 100-fold elevated levels of head activator over neighbouring tissue were found in tumors of the brain, especially in tumors of neural origin like astrocytoma and glioblastoma, but also in meningioma. Coincident with elevated tissue levels, an increased secretion into the general circulation was observed. Elevated levels of head activator in the blood were also observed in patients with tumors in peripheral locations, especially in tumors of gastrointestinal tract and/or of neuroendocrine origin. After tumor removal, the head activator levels in the blood dropped to normal values suggesting a possible role of head activator in neuroendocrine tumorigenesis.
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PMID:Elevated levels of head activator in human brain tumors and in serum of patients with brain and other neurally derived tumors. 322 43


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