Document Detail


Topoisomerase II gene mutations in tumors and tumor cell lines with microsatellite instability.
MedLine Citation:
PMID:  15533598     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genetic or epigenetic inactivation of the DNA mismatch repair genes in tumor precursor cells results in a strong mutator phenotype, known as the microsatellite mutator phenotype (MMP), or microsatellite instability (MSI). This mutator phenotype causes mutations in genes responsible for the regulation of cell growth and survival/death and thus promotes the development and progression of tumors. In the present study, we examined the DNA topoisomerase II genes (topIIalpha and topIIbeta) as mutational targets for MMP. We screened 10 MSI-positive human tumor cell lines and 30 MSI-positive colorectal tumors for mutations within the entire coding region of the topIIalpha gene and two coding poly(A)7 sequences of topIIbeta. Mutations in either the topIIalpha or topIIbeta gene were found with an overall frequency of 18% (in 10% of the primary tumors and in 44% of the cell lines). This indicates that modulation of the DNA topoisomerase II (TOPII) activity may be important for the development of MSI-positive cancer.
Authors:
Elena I Shagisultanova; Zhe Piao; Hai-Ri Li; Sergei R Malkhosyan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer letters     Volume:  216     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-09     Completed Date:  2005-02-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  221-6     Citation Subset:  IM    
Affiliation:
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Colonic Neoplasms / enzymology,  genetics*
DNA Topoisomerases, Type II / genetics*,  metabolism
Female
Frameshift Mutation
Humans
Male
Microsatellite Repeats / genetics
Mutation, Missense
Neoplasm Proteins / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/Neoplasm Proteins; EC 5.99.1.3/DNA Topoisomerases, Type II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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