Document Detail


The relationship between spontaneous telomere loss and chromosome instability in a human tumor cell line.
MedLine Citation:
PMID:  11228547     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chromosome instability plays an important role in cancer by promoting the alterations in the genome required for tumor cell progression. The loss of telomeres that protect the ends of chromosomes and prevent chromosome fusion has been proposed as one mechanism for chromosome instability in cancer cells, however, there is little direct evidence to support this hypothesis. To investigate the relationship between spontaneous telomere loss and chromosome instability in human cancer cells, clones of the EJ-30 tumor cell line were isolated in which a herpes simplex virus thymidine kinase (HSV-tk) gene was integrated immediately adjacent to a telomere. Selection for HSV-tk-deficient cells with ganciclovir demonstrated a high rate of loss of the end these "marked" chromosomes (10-4 events/cell per generation). DNA sequence and cytogenetic analysis suggests that the loss of function of the HSV-tk gene most often involves telomere loss, sister chromatid fusion, and prolonged periods of chromosome instability. In some HSV-tk-deficient cells, telomeric repeat sequences were added on to the end of the truncated HSV-tk gene at a new location, whereas in others, no telomere was detected on the end of the marked chromosome. These results suggest that spontaneous telomere loss is a mechanism for chromosome instability in human cancer cells.
Authors:
B Fouladi; L Sabatier; D Miller; G Pottier; J P Murnane
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  2     ISSN:  1522-8002     ISO Abbreviation:  Neoplasia     Publication Date:    2000 Nov-Dec
Date Detail:
Created Date:  2001-03-06     Completed Date:  2002-04-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  540-54     Citation Subset:  IM; S    
Affiliation:
Radiation Oncology Research Laboratory, University of California, San Francisco, 1855 Folsom Street, MCB 200, San Francisco, CA 94103, USA.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Blotting, Southern
Chromosome Aberrations
Chromosomes, Human / genetics*
DNA, Neoplasm / analysis
Herpesvirus 1, Human / genetics,  metabolism
Humans
In Situ Hybridization, Fluorescence
Karyotyping
Mitosis
Molecular Sequence Data
Plasmids / genetics
Sequence Homology, Nucleic Acid
Telomere / chemistry,  genetics*
Thymidine Kinase / genetics
Transfection
Tumor Cells, Cultured / physiology
Urinary Bladder Neoplasms / genetics*
Grant Support
ID/Acronym/Agency:
ES07106/ES/NIEHS NIH HHS; R01 CA69044/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Neoplasm; EC 2.7.1.21/Thymidine Kinase
Comments/Corrections

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