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

We have investigated 234 tumors of the central nervous system for amplification of 9 different loci from 12q13-14 and report that about 15% of the anaplastic astrocytomas and glioblastomas show amplification at this chromosomal region. The genes most frequently amplified were CDK4 and SAS (18 of 19 cases). MDM2 was coamplified with CDK4 and SAS in 11 tumors while one glioblastoma showed only MDM2 amplification. Some amplicons additionally included GADD153 (9 cases), GLI (6 cases), A2MR (3 cases), and the anonymous locus D12S8 (2 cases). Either MDM2 or CDK4 and SAS showed the highest amplification level in each individual amplicon and amplification of these genes was consistently accompanied by strong overexpression. Our results thus suggest CDK4, SAS, and MDM2 as main targets for the amplification; however, the possibility exists that all amplicons share a common amplified region between MDM2 and CDK4/SAS which might contain one or more as yet unidentified genes.
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PMID:Amplification of multiple genes from chromosomal region 12q13-14 in human malignant gliomas: preliminary mapping of the amplicons shows preferential involvement of CDK4, SAS, and MDM2. 804 75

Gliomas represent the largest group of primary brain tumors in adults. The astrocytic variants are the most common and the adult forms are histologically stratified into three malignancy grades. Of these glioblastoma is the most common and the most malignant; it has also been best studied by molecular genetics and cytogenetics. Double-minute chromosomes, known to represent amplified genes, are found in 50% of glioblastomas. Amplified genes are not detected in the most benign of the astrocytomas. Many genes have been shown to be amplified in more than single cases of gliomas and these include EGFR, CDK4, SAS, MDM2, GLI, PDGFAR, MYC, N MYC, MYCL1, MET, GADD153, and KIT. The most commonly amplified genes in glioblastomas are EGFR (in approximately 40%), CDK4, and SAS (in approximately 15%). The remainder of the genes are amplified at lower frequency. The best mapped amplicon in gliomas involves the 12q13-14 region. The amplicon is of undetermined size, encompasses a number of genes, and may be rearranged. It occurs in 15% of glioblastomas and almost always includes the CDK4 and SAS genes, in about 10% of tumors the MDM2 gene, and at lower frequency GLI, GADD153, and A2MR. All but A2MR are overexpressed if amplified. The amplified EGFR gene is frequently rearranged, resulting in changes in the regions of the transcript that codes for the extracellular domain. The resultant receptor is constitutively activated. These findings provide examples of the impact the use of modern molecular biological techniques has had on our understanding of oncogenic mechanisms in gliomas.
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PMID:Gene amplification in human gliomas. 858 64

We have reported previously that about 15% of anaplastic astrocytomas and glioblastomas show amplification and overexpression of one or more genes from chromosomal segment 12q13-q15 (G. Reifenberger et al., Cancer Res., 54, 4299-4303, 1994). The genes most frequently amplified and overexpressed were CDK4 (with coamplification of SAS) and MDM2. Because individual malignant gliomas showed CDK4/SAS amplification but no MDM2 amplification and vice versa, the possibility remained of a common amplification target gene located between CDK4 and MDM2. We have addressed this question by performing a detailed amplicon mapping of a series of 24 primary malignant gliomas and two glioblastoma cell lines with 12q13-q15 amplification. All tumors and cell lines were analyzed at eight gene loci and six anonymous loci from 12q13-q15, including seven loci located between CDK4 and MDM2. These studies revealed two centers of amplification, one at CDK4/SAS and the other at MDM2. A number of loci located close to either MDM2 or CDK4/SAS, including the genes GADD153, GLI, RAP1B, A2MR, and IFNG, were found to be coamplified in some tumors but not overexpressed consistently. All amplicons were discontinuous between CDK4/SAS and MDM2. Our results thus exclude a common amplification target between CDK4/SAS and MDM2 and provide additional evidence that these genes represent two independent targets of selection.
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PMID:Refined mapping of 12q13-q15 amplicons in human malignant gliomas suggests CDK4/SAS and MDM2 as independent amplification targets. 891 48