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Open Access Research article

Telomere shortening correlates to dysplasia but not to DNA aneuploidy in longstanding ulcerative colitis

Mariann Friis-Ottessen15*, Laila Bendix2, Steen Kølvraa2, Solveig Norheim-Andersen3, Paula M De Angelis1 and Ole Petter F Clausen14

Author Affiliations

1 Department of Pathology, Division of Diagnostics and Intervention, Oslo University Hospital, Rikshospitalet, Oslo, Norway

2 Danish Aging Research Center, University of Southern Denmark, Vejle, Denmark

3 Department of Pathology, Akershus University Hospital, Division of Medicine and Laboratory Sciences, University of Oslo, Oslo, Norway

4 Department of Pathology, University of Oslo, Oslo, Norway

5 OUS HF Rikshospitalet, Postboks 4950, Nydalen 0424 Oslo, Norway

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BMC Gastroenterology 2014, 14:8  doi:10.1186/1471-230X-14-8

Published: 9 January 2014

Abstract

Background

Ulcerative colitis (UC) is a chronic, inflammatory bowel disease which may lead to dysplasia and adenocarcinoma in patients when long-lasting. Short telomeres have been reported in mucosal cells of UC patients. Telomeres are repetitive base sequences capping the ends of linear chromosomes, and protect them from erosion and subsequent wrongful recombination and end-to-end joining during cell division. Short telomeres are associated with the development of chromosomal instability and aneuploidy, the latter being risk factors for development of dysplasia and cancer. Specifically, the abrupt shortening of one or more telomeres to a critical length, rather than bulk shortening of telomeres, seems to be associated with chromosomal instability.

Methods

We investigated possible associations between dysplasia, aneuploidy and telomere status in a total of eight lesions from each of ten progressors and four nonprogressors suffering from longstanding UC. We have analyzed mean telomere length by qPCR, as well as the amount of ultra-short telomeres by the Universal STELA method.

Results

An increased amount of ultra-short telomeres, as well as general shortening of mean telomere length are significantly associated with dysplasia in longstanding UC. Furthermore, levels of ultra-short telomeres are also significantly increased in progressors (colons harbouring cancer/dysplasia and/or aneuploidy) compared to nonprogressors (without cancer/dysplasia/aneuploidy), whereas general shortening of telomeres did not show such associations.

Conclusions

Our data suggest that ultra-short telomeres may be more tightly linked to colorectal carcinogenesis through development of dysplasia in UC than general telomere shortening. Telomere status was not seen to associate with DNA aneuploidy.

Keywords:
Ulcerative colitis; Ultra-short telomeres; Mean telomere length; DNA-aneuploidy; Dysplasia