The Relationship Between Spontaneous Telomere Loss and Chromosome Instability in a Human Tumor Cell Line
Open accessAbstract
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.
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Telomere loss at individual chromosome ends is sufficient to produce many rearrangements seen in telomere crisis and cancer, including amplifications, LOH, translocations, chromosome non-disjunction, and formation of isochromosomes and ring chromosomes.
“Telomere loss at individual chromosome ends is sufficient to produce many of the rearrangements seen in telomere crisis and in cancer, including amplifications, LOH, translocations, chromosome non-disjunction during mitosis, and the formation of isochromosomes and ring chromosomes170,172.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [170]
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DNA REPAIR PATHWAYS INVOLVED IN THE FORMATION OF ANAPHASE BRIDGES
Açılan, C. (2007) · D-Scholarship@Pitt (University of Pittsburgh)
- Authors
- Fouladi, B., Sabatier, L., Miller, D., Pottier, G., & Murnane, J. P.
- Affiliations
- University of California, San Francisco (US)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Corresponding author
- Murnane, John P.
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2000
- Volume
- 2
- Issue
- 6
- Pages
- 540-554
- ISSN
- 1476-5586 (ISSN-L)
- PMC
- PMC1508089
- OpenAlex
- W1968067337
- Cited by
- 96
- References
- 70
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 4
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neoplasia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Cancer Institute (R01CA069044, R01 CA69044, CA69044)
- National Institute of Environmental Health Sciences (ES 07106, T32ES007106)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- telomere loss, chromosomal instability, HSV-tk gene, telomeric repeats, chromosome end protection
- MeSH terms
- Base Sequence, Urinary Bladder Neoplasms, Chromosome Aberrations, Chromosomes, Human, DNA, Neoplasm, Humans, Karyotyping, Mitosis, Molecular Sequence Data, Plasmids, Sequence Homology, Nucleic Acid, Thymidine Kinase, Transfection, Tumor Cells, Cultured, Blotting, Southern, Telomere, In Situ Hybridization, Fluorescence, Herpesvirus 1, Human
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