Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown frequent allelic losses of chromosomes 9p, 10, 17p, and 22q in glial tumors. Other researchers have briefly reported that glial tumors may also show allelic losses of chromosome 19, suggesting a putative tumor suppressor gene locus on this chromosome (D. T. Ransom et al., Proc. Am. Assoc. Cancer Res., 32:302, 1991). To evaluate whether loss of chromosome 19 alleles is common in glial tumors of different types and grades, we performed Southern blot restriction fragment length polymorphism analysis for multiple chromosome 19 loci in 122 gliomas from 116 patients. Twenty-nine tumors had loss of constitutional heterozygosity of 19q, and four tumors had partial deletions of 19q. Allelic losses on 19q were restricted to grade III anaplastic astrocytomas (4/9) and grade IV glioblastomas (11/46), grade II oligodendrogliomas (2/5) and grade III anaplastic oligodendrogliomas (2/2), and grade II (5/8) and grade III (5/7) mixed oligoastrocytomas. These data demonstrate genetic similarities between astrocytomas, oligodendrogliomas, and mixed glial tumors and indicate the presence of a glial tumor suppressor gene on chromosome 19q.
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PMID:Evidence for a tumor suppressor gene on chromosome 19q associated with human astrocytomas, oligodendrogliomas, and mixed gliomas. 135 11

Loci on chromosome 9p are frequently deleted in several malignant tumors, suggesting the presence of putative tumor suppressor genes. The MTS1/p16 and MTS2/p15 genes on 9p are considered to be candidates. Binding of p15 and p16 cell cycle-regulatory proteins to the cyclin dependent protein kinase CDK4 inhibits CDK4/cyclin D dependent phosphorylation of retinoblastoma protein. We analysed the DNAs from 37 gliomas of several grades of malignancy for allelic loss of chromosome 9p and aberrations of the MTS1/p16 and MTS2/p15 genes. We detected losses of one allele and homozygous deletions at loci, including those of the MTS1/p16 and MTS2/p15 genes, in 10 and 3 tumors, respectively. However, we did not detect any tumor-specific mutation in the two genes. The CDK4 gene was amplified in two malignant gliomas without homozygous deletion of the MTS1/p16 and MTS2/p15 genes and one malignant glioma with an allelic loss of the genes. These data suggest that aberrations of the genes coding for components of the cell cycle-regulatory system occurred in at least 15 of 37 gliomas.
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PMID:Homozygous deletion of the MTS1/p16 and MTS2/p15 genes and amplification of the CDK4 gene in glioma. 747 35

The frequent allelic loss of chromosome 19q in human gliomas suggests that 19q harbors a tumor suppressor gene that is integral to glioma tumorigenesis. Our initial deletion mapping of this gene localized the common region of deletion to the distal long arm, 19q13.2-13.4. To bracket the putative tumor suppressor gene further, we have studied this region in 55 gliomas, using loss of heterozygosity studies for 11 well mapped, highly informative microsatellite polymorphisms that cover this area: D19S178; BCL3; APOC2; ERCC1; DM; D19S112; HRC; D19S246; KLK; D19S180; and D19S254 (from centromeric to telomeric). Twenty astrocytic, oligodendroglial, and mixed gliomas had deletions affecting this region. Of nine partial deletions, two cases maintained heterozygosity at APOC2 while showing allelic loss at the more telomeric markers, ERCC1 and DM, while five cases maintained heterozygosity at HRC but lost the more centromeric markers, D19S112 and DM. Nine cases lost the entire D19S178 to D19S254 region. Three astrocytic gliomas, including one with an interstitial deletion, had terminal deletions of 19q13.4. The minimum area of overlap shared by the interstitial deletions is between APOC2 and HRC, including ERCC1, DM, and D19S112. These findings suggest that the glioma tumor suppressor gene maps to an approximately 8-cM/5-megabase region on 19q13.2-13.3 between the proximal marker APOC2 and the distal marker HRC. Among the DNA repair/DNA metabolism genes on chromosome 19q, ERCC1, LIG1, and perhaps ERCC2 are within the common area of deletion; XRCC1 is centromeric and is therefore excluded as a candidate.
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PMID:The putative glioma tumor suppressor gene on chromosome 19q maps between APOC2 and HRC. 806 76

There is evidence that a putative glioma tumor suppressor locus resides on the long arm of chromosome 19. We present data on 161 gliomas from 156 patients, which were studied by microsatellite analysis for loss of heterozygosity (LOH) on chromosome 19. Eight loci on the long arm and 2 loci on the short arm of chromosome 19 were examined. LOH on 19q was observed in 3/19 astrocytomas (WHO grade II), 12/27 anaplastic astrocytomas (WHO grade III), 16/76 cases of glioblastoma multiforme WHO (grade IV), 4/9 oligodendrogliomas (WHO grade II), 3/5 anaplastic oligodendrogliomas (WHO grade III), 5/9 mixed oligo-astrocytomas (WHO grade II) and 8/10 anaplastic oligo-astrocytomas (WHO grade III). While 31 of the tumors with LOH on chromosomal arm 19q exhibited allelic loss at every informative locus, 20 tumors showed terminal or interstitial deletions. In contrast to astrocytomas and glioblastomas, tumors with an oligodendroglial component had predominantly lost the entire long arm of chromosome 19. The common region of overlap in gliomas was located on 19q13.2-q13.4 between the markers D19S178 and D19S180. Our data confirm the involvement of a putative tumor suppressor gene on chromosomal arm 19q in gliomas and assign this gene to 19q13.2-q13.4.
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PMID:Deletion mapping of chromosome 19 in human gliomas. 819 74

The past few years have seen remarkable progress in understanding the molecular genetic basis of glioma formation. Affected oncogenes and tumor suppressor genes have been identified and putative tumor suppressor loci have been mapped. These studies have illustrated distinct molecular pathways for different glial neoplasms. We summarize the findings of an ongoing study initiated to characterize human gliomas on a molecular basis. The data are compiled from 150 astrocytic, oligodendroglial, and mixed gliomas that were assessed for genomic alterations characteristic of these neoplasms, i.e., loss of portions of chromosomes 1p, 9p, 10, 17p, 17q, and 19q, mutations of the p53 tumor suppressor gene, and amplification of the EGF receptor (EGFR) gene. Our findings support the hypothesis that distinct genetic pathways result in the formation of astrocytic and oligodendroglial neoplasms of different malignancy grades, and that glioblastoma multiforme may be subdivided into genetically distinct subsets. Such findings may not only lead to a better understanding of neoplastic transformation in glial cells, but may also have a major impact on clinical neuro-oncology.
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PMID:Molecular pathways in the formation of gliomas. 858 67

This review examines the apparently paradoxical conversion of transforming growth factor beta's (TGFbeta) regulatory role as a growth inhibitor among normal glial cells to that of a progression factor among glioblastomas (GM). In vitro, TGFbeta functions as an autocrine growth inhibitor of near-diploid gliomas of any grade. In contrast, hyperdiploid glioblastoma multiforme (HD-GM) cultures proliferate in response to TGFbeta, which is mediated by induction of platelet-derived growth factor B chain (PDGF-BB). The dominant hypothesis of TGFbeta's pathogenetic association with malignant transformation has been predicated upon acquisition of resistance to its growth inhibitory effects. However, the lack of obvious correlation with TGFbeta receptor (TbetaR) expression (or loss) between the HD-GM and the TGFbeta-inhibited GM cultures suggests the existence of intrinsically opposed regulatory mechanisms influenced by TGFbeta. The mechanism of conversion might be explained either by the loss of a putative tumor suppressor gene (TSG) which mediates TGFbeta's inhibition of growth or by enhancement of an active oncogenic pathway among the HD-GM. The frequency of mutations within glioma-associated TSG, such as TP53 and RB, suggests that defects in TGFbeta's inhibitory signaling pathway may have analogous effects in the progression to HD-GM, and TGFbeta's conversion to a mitogen. Alternative sites of inactivation which might explain the loss of TGFbeta's inhibitory effect include inactivating mutation/loss of the TbetaR type II, alterations in post-receptor signal transmission or the cyclin/cyclin dependent kinase system which regulates the phosphorylation of pRB. Loss or inactivation of a glial TSG with a consequent failure of inhibition appears to allow TGFbeta's other constitutive effects, such as induction of c-sis, to become functionally dominant. Mechanistically, TGFbeta's conversion from autocrine inhibitor to mitogen promotes 'clonal dominance' by conferring a Darwinian advantage to the hyperdiploid subpopulations through qualitative and quantitative differences in its modulation of PDGF-A and c-sis, with concomitant paracrine inhibition of competing, near-diploid elements.
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PMID:The role of transforming growth factor beta in glioma progression. 952 12

The PTEN gene is involved in 10q23 deletions in several types of cancer, including glioma, melanoma, endometrial and prostate carcinomas. The PTEN gene product is a dual-specificity phosphatase with putative tumor suppressor function. Deletions and rearrangements of 10q22-25 have been reported in approximately 5%-10% of non-Hodgkin's lymphomas (NHLs), raising the possibility of PTEN involvement in these tumors. In order to address this question, we analyzed a panel of NHLs (n = 74) representative of the main histologic subtypes for mutations and homozygous deletions of PTEN. We report somatic coding/splice site mutations in 20% (2 of 10) of Burkitt's lymphoma cell lines and in 3% (2 of 64) of primary NHL cases analyzed. No homozygous deletions were found in these tumors. Interestingly, this study showed that cytogenetically characterized NHL cases (n = 6) with 10q22-q25 abnormalities displayed neither biallelic deletions nor mutations of PTEN. These results suggest that a tumor suppressor gene distinct from PTEN may be involved in 10q deletions in this subgroup of NHL cases.
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PMID:Analysis of PTEN mutations and deletions in B-cell non-Hodgkin's lymphomas. 1009 30

Allelic alterations of chromosomes 1 and 19 are frequent events in human diffuse gliomas and have recently proven to be strong predictors of chemotherapeutic response and prolonged survival in oligodendrogliomas (Cairncross et al., 1998; Smith et al., submitted). Using 115 human diffuse gliomas, we localized regions of common allelic loss on chromosomes 1 and 19 and assessed the association of these deletion intervals with glioma histological subtypes. Further, we evaluated the capacity of multiple modalities to detect these alterations, including loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH). The correlation coefficients for detection of 1p and 19q alterations, respectively, between modalities were: 0.98 and 0.87 for LOH and FISH, 0.79 and 0.60 for LOH and CGH, and 0.79 and 0.53 for FISH and CGH. Minimal deletion regions were defined on 19q13.3 (D19S412-D19S596) and 1p (D1S468-D1S1612). Loss of the 1p36 region was found in 18% of astrocytomas (10/55) and in 73% (24/33) of oligodendrogliomas (P < 0.0001), and loss of the 19q13.3 region was found in 38% (21/55) of astrocytomas and 73% (24/33) of oligodendrogliomas (P = 0.0017). Loss of both regions was found in 11% (6/55) of astrocytomas and in 64% (21/33) of oligodendrogliomas (P < 0.0001). All gliomas with LOH on either 1p or 19q demonstrated loss of the corresponding FISH probe, 1p36 or 19q13.3, suggesting not only locations of putative tumor suppressor genes, but also a simple assay for assessment of 1p and 19q alterations as diagnostic and prognostic markers.
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PMID:Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. 1043 96

Deletion of chromosome 10 is one of the most common chromosomal alterations in glioma. At 10p15, the telomeric region of the short arm of chromosome 10, loss of heterozygosity (LOH) has been frequently observed by microsatellite analysis, suggesting the presence of a tumor suppressor gene. We examined LOH in 34 gliomas on chromosome 10, and frequent LOH on 10p was detected on 10p15, in agreement with deletion mapping studies on chromosome 10. We then constructed a bacterial artificial chromosome (BAC) clone contig covering the critical region, which spanned the interval between D10S249 and D10S533 on 10p15. The map contained 68 BAC clones connected by 74 sequenced tag sites (STSs) and covered approximately 2.7 Mb, with one gap. A total of 74 STSs, including 6 microsatellite markers, 29 expressed sequenced tags (ESTs), and 39 BAC end STSs, were physically arranged. Twenty-eight ESTs were mapped in the interval between D10S249 and D10S559 (approximately 1200 kb), and another EST was mapped in the interval between D10S559 and D10S533 (approximately 1300 kb). This sequence-ready BAC clone contig map will be a basic resource for high-quality sequencing and positional cloning of the putative tumor suppressor gene at 10p15 in glioma.
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PMID:A sequence-ready BAC clone contig of human chromosome 10p15 spanning the loss of heterozygosity region in glioma. 1093 48

A putative tumor suppressor, the PTEN gene at chromosome 10q23. was identified and found to be mutated in many different human tumors. PTEN was recently found to be also involved in focal cell adhesion and cell migration. To identify the role of PTEN gene in malignant gliomas. we used PCR-SSCP and direct sequencing methods to examine 44 malignant gliomas comprising 29 cases without and 15 cases with meningeal gliomatosis. In malignant gliomas without meningeal gliomatosis, 2/29 (7%) of the cases showed alteration of the PTEN gene. In contrast, 5/15 (33%) of malignant gliomas with meningeal gliomatosis cases showed this alteration. These findings indicate that PTEN gene mutation contributes not only to the neoplastic evolution in gliomas but also to the meningeal dissemination of glioma cells.
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PMID:PTEN mutations in malignant gliomas and their relation with meningeal gliomatosis. 1167 26


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