Relationship between telomere shortening, genetic instability, and site of tumour origin in colorectal cancers
Open Access
- 13 April 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 102 (8), 1300-1305
- https://doi.org/10.1038/sj.bjc.6605644
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 (Pr=−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.Keywords
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