Genotypic and phenotypic changes in the colonic mucosa of patients suffering from longstanding ulcerative colitis
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AbstractUlcerative colitis (UC) is an inflammatory bowel disease, associated with increased lifetime risk of developing colorectal cancer. UC-associated cancers progress through increasing levels of dysplasia, accompanied by important molecular changes, such as chromosomal instability and aneuploidy. Aneuploidy is a common feature in UC-colonic mucosa, and is often seen to precede dysplasia and cancer. Approximately 10 % of UC-patients will develop malignancies through the colon within 10 years of disease duration. These patients have increased risk of developing cancer, and are termed progressors. Patients with no malignant changes to the colonic mucosa are termed non-progressors, and have no increased risk of cancer development. The molecular mechanisms underlying malignant progression in UC are not fully elucidated, but are suggested to involve increasing degrees of chromosomal instability, telomere shortening and a defect spindle assembly checkpoint. Chronic inflammation elevates the level of oxidative stress. Oxidative stress can create ultra-short telomeres through single-or double strand chromosome breaks. A single ultra-short telomere may induce aneuploidy. We investigated the amounts of ultra-short telomeres in UC-colonic mucosal cells of both progressors and nonprogressors, applying a method for estimating the amount of ultra-short telomeres, the Universal STELA. We found that progressors have higher levels of ultra-short telomeres in the colonic mucosal lining compared to non-progressors. Our results provide new information concerning the investigation of the molecular underpinnings of cancer progression in UC, and may be of use in detecting a progressor at an early stage of the disease development.
List of papers
|Paper I: Telomere shortening correlates to dysplasia but not to DNA aneuploidy in longstanding ulcerative colitis Friis-Ottessen M., Bendix L., Kølvraa S., Norheim-Andersen S., De Angelis P. M., Clausen O. P. BMC Gastroenterology 2014, 14:8 (9 January 2014). This is an open access article distributed under the terms of the Creative Commons Attribution License. The published version of this paper is available at: https://doi.org/10.1186/1471-230X-14-8|
|Paper II: TP53/p53 alterations and Aurora A expression in progressor and nonprogressor colectomies from patients with longstanding ulcerative colitis. Friis-Ottessen M., Burum-Auensen E., Schjølberg A. R., Ekstrøm P.O., Norheim-Andersen S., Clausen O.P., De Angelis P. M. Author version, published in: Int J Mol Med. 2015 Jan;35(1):24-30. This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The published version of this paper is available at: https://doi.org/10.3892/ijmm.2014.1974|
|Paper III: Reduced hTERT protein levels are associated with DNA aneuploidy in the colonic mucosa of patients suffering from longstanding ulcerative colitis Friis-Ottessen M., De Angelis P. M., Schjølberg A. R., Norheim-Andersen S., Clausen O. P. Int J Mol Med. Jun 2014; 33(6): 1477–1483. This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The published version of this paper is available at: https://doi.org/10.3892/ijmm.2014.1708|