Cyclin-dependent kinase 6 (CDK6) amplification in human gliomas identified using two-dimensional separation of genomic DNA

DNA amplification is a common mechanism invoked by many human tumors to elicit overexpression of genes whose products are involved in drug resistance or cell proliferation. Although amplified regions in tumor DNA may exceed several megabases in size, segments of amplicons with a high probability of...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1997-04, Vol.57 (7), p.1250-1254
Main Authors: COSTELLO, J. F, PLASS, C, ARAP, W, CHAPMAN, V. M, HELD, W. A, BERGER, M. S, SU HUANG, H.-J, CAVENEE, W. K
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
Blotting, Southern
Blotting, Western
Brain Neoplasms - genetics
Chromosomes, Human, Pair 7
Cloning, Molecular
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinases
DNA - analysis
Electrophoresis, Gel, Two-Dimensional - methods
Gene Amplification
Glioma - genetics
Humans
Medical sciences
Molecular Sequence Data
Neurology
Protein-Serine-Threonine Kinases - genetics
Tumors of the nervous system. Phacomatoses
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Summary:DNA amplification is a common mechanism invoked by many human tumors to elicit overexpression of genes whose products are involved in drug resistance or cell proliferation. Although amplified regions in tumor DNA may exceed several megabases in size, segments of amplicons with a high probability of containing gene sequences may be amenable to detection by restriction landmark genomic scanning (RLGS), a high-resolution DNA analysis that separates labeled NotI fragments in two dimensions. Here, we tested this by applying RLGS to matched samples of glioma and normal brain DNA and found tumor-specific amplification of the gene encoding cyclin-dependent kinase 6 (CDK6), an observation not previously reported in human tumors. The CDK6 gene has been localized to chromosome 7q21-22, but in the gliomas studied here, it was not coamplified with either the syntenic MET (7q31) or epidermal growth factor receptor (7p11-p12) genes, suggesting that this may be part of a novel amplicon in gliomas. We then corroborated this finding by identifying both amplification-associated and amplification-independent increases in CDK6 protein levels in gliomas relative to matched normal brain samples. These data implicate the CDK6 gene in genomic amplification and illustrate the potential of RLGS for the more general identification and cloning of novel genes that are amplified in human cancer.
ISSN:0008-5472
1538-7445