Telomere-related Genome Instability in Cancer
Open accessAbstract
The genomes of human carcinomas and several other tumor types are in an astonishing state of disarray.The extent of genome scrambling was only appreciated after development of high-resolution techniques.Spectral karyotyping (M-FISH, SKY) has painted a picture of extensive reshuffling of chromosome segments.Techniques that display the differences between normal and cancer genomes, combined with DNA microarrays (array-CGH, Pinkel et al. 1998; ROMA, Lucito et al. 2003), have revealed countless copy number changes.What is the origin of this genome instability?Recent findings make a compelling case for the view that genome instability in human cancer is largely rooted in telomere dysfunction.Dysfunctional telomeres can explain most genome alterations observed in human cancer (Fig. 1).Moreover, the telomere-shortening process that gives rise to dysfunctional telomeres takes place in the majority of human somatic cells, potentially explaining genome instability in many different human tumor types.Finally, a brief period of telomere dysfunction early in tumorigenesis can explain the transient nature of cancer genome instability.New data relating to these issues are discussed below. TELOMERES AND THEIR FUNCTIONAL COLLAPSEThe molecular features of human telomeres are now understood in sufficient depth to permit formulation of a working model for how these elements protect chromosome ends (Fig. 2).In human cells, chromosomes termi- Telomere-related Genome Instability in Cancer
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The transient nature of telomere crisis as a source of genome instability in cancer is attractive because it avoids a persistent mutator phenotype that could hamper cell proliferation.
“The brief, or at least transient, episode of genomic instability offered by dysfunctional telomeres avoids a persistent mutator phenotype that might hamper cell proliferation10.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [10]
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- Authors
- DE LANGE, T.
- Venue
- Cold Spring Harbor Symposia on Quantitative Biology
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-01-01
- Volume
- 70
- Issue
- 0
- Pages
- 197-204
- ISSN
- 0091-7451 (ISSN-L)
- 1943-4456
- OpenAlex
- W2144794152
- Cited by
- 182
- References
- 13
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 5 · 2019: 8 · 2018: 7 · 2017: 11 · 2016: 16 · 2015: 12 · 2014: 17 · 2013: 7 · 2012: 10
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Symposia on Quantitative Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Breast Cancer Research Foundation
- National Institutes of Health (GM49046)
- National Institute on Aging (AG16642)
- National Cancer Institute (R01CA076027, CA76027)
- National Institute of General Medical Sciences (GM 49046)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- telomere dysfunction, genomic instability, cancer, telomere shortening, copy number alterations, chromosomal rearrangements, tumor suppressor, telomere protection, somatic cells, carcinogenesis
- MeSH terms
- Aneuploidy, Animals, DNA Damage, DNA Repair, Gene Amplification, Humans, Chromosome Inversion, Models, Genetic, Mutation, Neoplasms, Polyploidy, Translocation, Genetic, Telomere, Gene Deletion, Mice, Knockout, Telomerase, Chromosome Breakage, Loss of Heterozygosity, Genomic Instability, Mice
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