Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Von Recklinghausen neurofibromatosis (NF1) is a common autosomal dominant disorder mapped to 17q11.2 and typically characterized by the occurrence of neural crest-derived tumors. The gene has recently been cloned using reverse genetics or "positional cloning" approaches. Its function, however, remains unknown. We have performed cytogenetic and molecular analyses on 9 malignant tumors from NF1 patients to look for loss of alleles or chromosome rearrangements involving chromosome 17 to test the hypothesis that the NF1 gene acts as a recessive "tumor suppressor" gene. Loss of alleles on this chromosome was detected for 3 of 9 malignant tumors. Two peripheral nerve sheath tumors showed allele loss at informative loci on both the long and short arms of chromosome 17. In contrast, a glioblastoma with focal gliosarcoma showed loss of heterozygosity on the short arm of chromosome 17 only, and not at loci on the long arm. One nerve sheath tumor was previously shown by direct sequence analysis to have a point mutation at the TP53 locus at 17p13. These data support a role for the TP53 gene or other genes on the short arm of chromosome 17 in at least some malignancies in NF1. Six other neurofibrosarcomas showed no allele loss at informative loci on chromosome 17. Cytogenetic analysis was performed on 7 tumors, including 2 with allele loss. The two tumors with allele loss showed abnormal karyotypes while all others were normal. Southern blot and pulsed-field gel analysis using probes within or closely linked to the NF1 locus detected no gross deletions or rearrangements in the tumors studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular and cytogenetic analysis of tumors in von Recklinghausen neurofibromatosis. 190 41

Quantitative determination of human glioma-associated antigen in cerebrospinal fluids (CSFs) obtained from 66 patients with a variety of neurological diseases was performed by solid-phase radioimmunoassay with a monoclonal antibody (G-22). In this system, the minimum detectable amount of the antigen in the CSF was 8 ng/ml. It was demonstrated that CSF diagnosis of glioblastoma might be possible in the case of small tumors with a diameter of less than 2 cm. CSFs obtained from all 18 patients with glioma were positive and the level varied from 11.2 to 186.1 ng/ml. The antigen level in the cystic fluid of the tumor was higher than that in CSF. There was a tendency for the antigen level in CSF to be correlated with the tumor size and the type of histology. The malignant types of glioblastoma or medulloblastoma showed higher levels than the benign type of ependymoma and astrocytoma. Most types of non-gliomatous brain tumor were negative except immature teratoma, meningioma with central neurofibromatosis, and metastatic brain tumor from lung cancer. We also noted that tumor progression or regression of malignant glioma could be predicted by the monitoring of the antigen in the CSF.
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PMID:Radioimmunoassay of glioma-associated antigen in cerebrospinal fluid and its usefulness for the diagnosis and monitoring of human glioma. 191 50

In 1,491 autopsy cases with CNS tumors observed at the Pathological Institute of the Medical Academy of Erfurt in the period from 1953 to 1976 (54,946 autopsies) 72 cases (4.8%) with neurinomas were found. They comprise 67 solitary neurinomas, 1 bilateral acoustic neurinoma without other signs of neurofibromatosis, and 4 cases of neurofibromatosis with neurinomas of the CNS. Among the 68 cases with CNS neurinomas (neurofibromatoses excluded) 87% were acoustic neurinomas, 12% spinal tumors, and 1 case was located in the trigeminal nerve. In 60 (88%) of these 68 cases, the neurinoma was operated upon or clinically diagnosed, resp. The diameter of 18 (26%) neurinomas of the autopsy material was larger than 5 cm. Patients in the 6th decennium predominated in this series. The sex distribution revealed a preponderance of females over males (3:1). In 3 cases further CNS tumors (ependymoma, glioblastoma, meningioma) were found. Additionally, 3 cases had carcinomas of different localization (Table 5). Following tumors were seen in 9 cases of Morbus Recklinghausen with CNS involvement: 4 cases with multiple neurinomas, 3 meningiomas, 1 astrocytoma, 2 glioses and 1 angiomatous malformation (Table 6). Among 1,670 CNS tumors in biopsy material, 144 (8.6%) were neurinomas. 60% of them were located in the nervus acusticus, 40% spinally, mainly in the thoracic region. The 6th decennium was most affected, and females were more frequent than males (2:1) in our material. Nearly all CNS neurinomas were benign. Only 1 spinal tumors was classified as a malignant neurinoma. 2 of the 9 cases with Morbus Recklinghausen had malignant neurogenic tumors (neurofibrosarcomas).
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PMID:[Tumors of the central nervous system in biopsy and autopsy material. 7th communication: neurinomas and neurofibromatoses with CNS involvement]. 641 Jun 15

We have developed an exon-trapping system with a newly constructed trapping vector containing multiple cloning sites (designated pEXT2). The system revealed high sensitivity for trapping a control exon from several hundred kbp of DNA. We have applied the system to the cosmid clones located on human chromosome 21p11-q21, and identified two fragments highly homologous to neurofibromatosis 1 (NF1) gene and a clearly transcribed fragment hybridized with approximately 1.6 kb RNA from human brain and human glioblastoma A172 cell.
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PMID:An exon-trapping system with a newly constructed trapping vector pEXT2; its application to the proximal region of the human chromosome 21 long arm. 768 13

A glioblastoma that retained glial fibrillary acidic protein (GFAP) in culture has a break in the long arm of chromosome 17 at band 17q11.2. DNA inserted at this breakpoint came from chromosome bands 3p21, 3q23, 16q11.2, and 22q11.2. These chromosome fragments were inserted in band 17q11.2 proximal to the neurofibromatosis-1 (NF-1) gene and neu (HER2; erbB2) oncogene loci. The glioblastoma also contained a reciprocal translocation between 16p12 and 20p12. These structural abnormalities, previously undescribed in gliomas, were demonstrated by high-resolution chromosome banding, microdissection, and fluorescence in situ hybridization (FISH). Numerical changes typical of glioblastoma were present: gain of chromosome 7 and losses of chromosomes 10, 13, and 22. The complex chromosome origin of DNA inserted in this glioma chromosome is described. The association of two infrequent events in this single glioblastoma line, this complex insertion and retention of GFAP expression, is not likely to be a chance occurrence. It raises the possibility of an association between the two events.
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PMID:Chromosome breakpoint at 17q11.2 and insertion of DNA from three different chromosomes in a glioblastoma with exceptional glial fibrillary acidic protein expression. 864 40

The neurofibromatosis 2 (NF2) gene-encoded protein, named merlin, may function as a molecular linkage connecting cytoskeleton and plasma membrane. Merlin is thought to play a crucial role as a tumor suppressor not only in hereditary NF2-related tumors, but also in sporadic tumors such as schwannomas, meningiomas and gliomas. Using a merlin-expression vector system, we raised specific antiserum against merlin. We observed the intracellular distribution of merlin in cultured glioma cells, and further investigated merlin expression in 116 human brain tumors. Immunofluorescence microscopy revealed that merlin was localized beneath the cell membrane and concentrated at cell-to-cell adhesion sites, where actin filaments are densely associated with plasma membrane. By immunohistochemistry, none of the schwannomas from either NF2 patients or sporadic cases showed any immunoreactivity, while normal Schwann cells of cranial nerves were immunopositive. In meningiomas, merlin expression was frequently seen in the meningothelial subtype (8/10, 80%), but no expression could be detected in either the fibrous or the transitional variant. Most normal astrocytes were negative; however, reactive astrocytes often expressed merlin. Glioblastomas and anaplastic astrocytomas were found to be strongly positive, and focal positive staining was observed in fibrillary and pilocytic astrocytomas. Thus, the loss of merlin appears to be integral to schwannoma formation and the differential pathogenesis of meningioma subtypes. However, merlin alterations do not appear to play a critical role in either the tumorigenesis or malignant transformation of neoplastic astrocytes.
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PMID:Expression of neurofibromatosis 2 protein in human brain tumors: an immunohistochemical study. 908 53

Astrocytomas are the leading cause of brain cancer in humans. Because these tumours are highly infiltrative, current treatments that rely on targeting the tumour mass are often ineffective. A mouse model for astrocytoma would be a powerful tool for dissecting tumour progression and testing therapeutics. Mouse models of astrocytoma have been designed to express oncogenic proteins in astrocytes, but have had limited success due to low tumour penetrance or limited tumour progression. We present here a mouse model of astrocytomas involving mutation of two tumour-suppressor genes, Nf1 and Trp53. Humans with mutations in NF1 develop neurofibromatosis type I (NF1) and have increased risk of optic gliomas, astrocytomas and glioblastomas. The TP53 tumour suppressor is often mutated in a subset of astrocytomas that develop at a young age and progress slowly to glioblastoma (termed secondary glioblastomas, in contrast to primary glioblastomas that develop rapidly de novo). This mouse model shows a range of astrocytoma stages, from low-grade astrocytoma to glioblastoma multiforme, and may accurately model human secondary glioblastoma involving TP53 loss. This is the first reported mouse model of astrocytoma initiated by loss of tumour suppressors, rather than overexpression of transgenic oncogenes.
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PMID:Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects. 1097 61

The case of a 37-year-old woman is presented. Cutaneous neurofibromatosis was associated with a progressive course of multiple sclerosis. Unexpectedly, autopsy revealed a right hemispheric glioblastoma which was silent during her life.
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PMID:Neurofibromatosis and glioblastoma in a case of multiple sclerosis. 1178 59

We have constructed the first comprehensive microarray representing a human chromosome for analysis of DNA copy number variation. This chromosome 22 array covers 34.7 Mb, representing 1.1% of the genome, with an average resolution of 75 kb. To demonstrate the utility of the array, we have applied it to profile acral melanoma, dermatofibrosarcoma, DiGeorge syndrome and neurofibromatosis 2. We accurately diagnosed homozygous/heterozygous deletions, amplifications/gains, IGLV/IGLC locus instability, and breakpoints of an imbalanced translocation. We further identified the 14-3-3 eta isoform as a candidate tumor suppressor in glioblastoma. Two significant methodological advances in array construction were also developed and validated. These include a strictly sequence defined, repeat-free, and non-redundant strategy for array preparation. This approach allows an increase in array resolution and analysis of any locus; disregarding common repeats, genomic clone availability and sequence redundancy. In addition, we report that the application of phi29 DNA polymerase is advantageous in microarray preparation. A broad spectrum of issues in medical research and diagnostics can be approached using the array. This well annotated and gene-rich autosome contains numerous uncharacterized disease genes. It is therefore crucial to associate these genes to specific 22q-related conditions and this array will be instrumental towards this goal. Furthermore, comprehensive epigenetic profiling of 22q-located genes and high-resolution analysis of replication timing across the entire chromosome can be studied using our array.
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PMID:A full-coverage, high-resolution human chromosome 22 genomic microarray for clinical and research applications. 1244 6

We questioned whether children with optic pathway tumors (OPTs) have an increased frequency of other CNS tumors on the basis of experience with a number of such children treated at our institution. The medical records of all patients with OPTs treated at Golisano Children's Hospital at Strong at the University of Rochester from 1957 to 2000 were reviewed to determine the incidence of additional CNS tumors in these children and whether the occurrence of these other CNS tumors is associated with any risk factors. Twenty-six children had OPTs. Twelve of the 26 children had biopsy-proved tumors; the remaining 14 were diagnosed on the basis of CT or MRI scans. Eight of the 26 patients (31%) had a total of 11 additional CNS tumors. (One child had 2 additional CNS neoplasms, and a second child had 3.) Nine were biopsy proved (3 glioblastoma, 3 anaplastic astrocytoma, 3 low-grade astrocytoma), and 2 were diagnosed by imaging studies alone (acoustic neuromas). Eight of the 11 tumors occurred at a median of 5 years (0.8-25 years) subsequent to the diagnosis of the OPTs; 3 were diagnosed simultaneously with the OPT. Of the 17 children with neurofibromatosis (NF) and OPTs, 8 (47%) had additional CNS tumors, while none of the 9 children (0%) without NF had other CNS tumors (P = 0.023). There was no association between radiation treatment of the primary OPT and subsequent development of other CNS tumors in the group as a whole, or when the analysis was confined to children with NF. Despite this lack of statistical association, all 7 CNS tumors that occurred following radiation arose in irradiated areas. The risk of simultaneous or subsequent CNS tumors in children with NF and OPTs is high. These children should be closely monitored for the simultaneous or subsequent occurrence of other CNS tumors.
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PMID:Do children with optic pathway tumors have an increased frequency of other central nervous system tumors? 1267 83


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