Relationship between telomere shortening, genetic instability, and site of tumour origin in colorectal cancers
Open accessAbstract
BACKGROUND: Telomeres, located at chromosome ends, are progressively shortened during each cell cycle by replication-dependent loss of DNA termini. Although maintenance of telomere length is critical for cell-replicative potential and tumourigenesis, the erosion of telomeres can lead to genetic instability, a pivotal mechanism in the neoplastic process. PATIENTS AND METHODS: A total of 118 colorectal cancer (CRC) samples (53 right-colon, 30 left-colon, and 35 rectal tumours) and corresponding adjacent non-cancerous tissues were evaluated for telomere length, p53 mutation, and microsatellite instability (MSI). Telomere length was estimated by real-time PCR. RESULTS: Telomeres were significantly shorter in CRCs than in adjacent tissues, regardless of tumour stage and grade, site, or genetic alterations (P<0.0001). Moreover, in normal tissues, but not in tumours, telomere length inversely correlated with age (r=-0.24, P=0.017). Telomere length in CRCs did not differ with tumour progression or p53 status; however, in CRCs carrying the wild-type p53, telomeres were significantly shorter in tumours with MSI than in those with stable microsatellites (P=0.027). Furthermore, telomere length differed according to tumour location, being longer in rectal cancers (P=0.03). CONCLUSIONS: These findings suggest that telomere shortening is a key initial event in colorectal carcinogenesis. The extent of telomere erosion is related to tumour origin site and may be influenced by the mismatch repair pathway.
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While earlier findings suggested that rectal cancers had a tendency to bear longer telomeres, a formal correlation between telomere length and tumor location is still debated.
“Regarding TL and tumor location, while earlier findings suggested that rectal cancers had a tendency to bear longer telomeres [200], a formal correlation between TL and tumor location is still debated.”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [200]
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- Authors
- Rampazzo, E., Bertorelle, R., Serra, L., Terrin, L., Candiotto, C., Pucciarelli, S., Bianco, P. D., Nitti, D., & De Rossi, A.
- Affiliations
- University of Padua (IT)
- Istituto Oncologico Veneto (IT)
- Venue
- British Journal of Cancer
- Published
- 2010-04
- Volume
- 102
- Issue
- 8
- Pages
- 1300-1305
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2856015
- OpenAlex
- W2003751750
- Cited by
- 125
- References
- 42
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 9 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 7 · 2018: 9 · 2017: 4 · 2016: 6 · 2015: 14 · 2014: 16 · 2013: 11 · 2012: 13
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by-nc-sa)
- Funders
- Ministero della Salute
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- telomere shortening, colorectal cancer, genomic instability, microsatellite instability, TP53 mutation, rectal cancer, right-sided colon cancer, left-sided colon cancer, DNA mismatch repair, carcinogenesis, telomere length
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Intestinal Mucosa, Male, Middle Aged, Colorectal Neoplasms, Telomere, Telomerase, Genomic Instability
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