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Cited by 125Telomeres, Telomerase, and SenescenceGenetic factors in colorectal cancerCancer-related Molecular Pathways

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Relationship between telomere shortening, genetic instability, and site of tumour origin in colorectal cancers

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Rampazzo, E, Bertorelle, R, Serra, L, Terrin, L, Candiotto, C, Pucciarelli, S, Bianco, P Del, Nitti, D, De Rossi, A·2010·British Journal of Cancer
DOI 10.1038/sj.bjc.6605644PMC PMC2856015
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Abstract

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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Figure 1 Correlation between telomere lengths estimated by Southern blotting (Kb) and real-time PCR (T/S value). A significant correlation was found (r=0.860, P<0.0001), giving the mathematical relation y=1.53x+3.12.
Figure 1 Correlation between telomere lengths estimated by Southern blotting (Kb) and real-time PCR (T/S value). A significant correlation was found (r=0.860, P<0.0001), giving the mathematical relation y=1.53x+3.12.CC BY-NC-SA · PubMed Central
Figure 2 Relative telomere lengths, expressed as T/S values, in tumours (K) and adjacent normal mucosa (N) in (A) all samples, and (B) according to tumour stage I, II, III, or IV. Boxes and whiskers represent the 25th–75th and 10th–90th percentiles, respectively; the median is the central line in each box. *P<0.0001. (C) Correlation between age and relative telomere lengths in tumours and normal mucosa. (D) Receiver-operating characteristics (ROC) curve for telomere lengths in tumours and normal mucosa using T/S values. Sensitivity (y axis) was plotted against the false-positive fraction (100-specificity). The area under the ROC curve (AUC) is 0.91 (95% confidence intervals (CI) 0.87–0.95).
Figure 2 Relative telomere lengths, expressed as T/S values, in tumours (K) and adjacent normal mucosa (N) in (A) all samples, and (B) according to tumour stage I, II, III, or IV. Boxes and whiskers represent the 25th–75th and 10th–90th percentiles, respectively; the median is the central line in each box. *P<0.0001. (C) Correlation between age and relative telomere lengths in tumours and normal mucosa. (D) Receiver-operating characteristics (ROC) curve for telomere lengths in tumours and normal mucosa using T/S values. Sensitivity (y axis) was plotted against the false-positive fraction (100-specificity). The area under the ROC curve (AUC) is 0.91 (95% confidence intervals (CI) 0.87–0.95).CC BY-NC-SA · PubMed Central
Figure 3 Relative telomere lengths, expressed as T/S values, in tumours according to (A) mutated (n=49) or wild-type (n=69) p53 gene, and (B) high microsatellite instability (MSI-H) (n=28) or stable microsatellite (MSS) (90) status. (C) Relative telomere lengths, expressed as T/S values, in p53 mutated MSS (n=45), p53 wild-type MSI-H (n=24), and p53 wild-type MSS (n=45) tumours. Boxes and whiskers represent the 25th–75th and 10th–90th percentiles, respectively; the median is the central line in each box.
Figure 3 Relative telomere lengths, expressed as T/S values, in tumours according to (A) mutated (n=49) or wild-type (n=69) p53 gene, and (B) high microsatellite instability (MSI-H) (n=28) or stable microsatellite (MSS) (90) status. (C) Relative telomere lengths, expressed as T/S values, in p53 mutated MSS (n=45), p53 wild-type MSI-H (n=24), and p53 wild-type MSS (n=45) tumours. Boxes and whiskers represent the 25th–75th and 10th–90th percentiles, respectively; the median is the central line in each box.CC BY-NC-SA · PubMed Central
Figure 4 Relative telomere lengths, expressed as T/S values, in tumours according to the site of origin: right colon (n=53), left colon (n=30), rectum (n=35). Boxes and whiskers represent the 25th–75th and 10th–90th percentiles, respectively; the median is the central line in each box.
Figure 4 Relative telomere lengths, expressed as T/S values, in tumours according to the site of origin: right colon (n=53), left colon (n=30), rectum (n=35). Boxes and whiskers represent the 25th–75th and 10th–90th percentiles, respectively; the median is the central line in each box.CC BY-NC-SA · PubMed Central

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Metadata

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)
ORCID
Venue
British Journal of Cancer
Publisher
Springer Science and Business Media LLC
Published
2010-04
Volume
102
Issue
8
Pages
1300-1305
ISSN
  • 0007-0920 (ISSN-L)
  • 1532-1827
DOI
10.1038/sj.bjc.6605644
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
Licence
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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