Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia

Letsolo, B. T., Jones, R. E., Rowson, J., Grimstead, J. W., Keith, W. N. , Jenkins, G. J.S. and Baird, D. M. (2017) Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia. PLoS ONE, 12(3), e0174833. (doi:10.1371/journal.pone.0174833) (PMID:28362812) (PMCID:PMC5375150)

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Abstract

Barrett’s oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett’s oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information. The aim of this work was to use high-resolution telomere analysis to examine telomere dynamics in Barrett’s oesophagus. Telomere length analysis of XpYp, 17p, 11q and 9p, chromosome arms that contain key cancer related genes that are known to be subjected to copy number changes in Barrett’s metaplasia, revealed similar profiles at each chromosome end, indicating that no one specific telomere is likely to suffer preferential telomere erosion. Analysis of patient matched tissues (233 samples from 32 patients) sampled from normal squamous oesophagus, Z-line, and 2 cm intervals within Barrett’s metaplasia, plus oesophago-gastric junction, gastric body and antrum, revealed extensive telomere erosion in Barrett’s metaplasia to within the length ranges at which telomere fusion is detected in other tumour types. Telomere erosion was not uniform, with distinct zones displaying more extensive erosion and more homogenous telomere length profiles. These data are consistent with an extensive proliferative history of cells within Barrett’s metaplasia and are indicative of localised clonal growth. The extent of telomere erosion highlights the potential of telomere dysfunction to drive genome instability and clonal evolution in Barrett’s metaplasia.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Keith, Professor Nicol and Jenkins, Professor Gareth
Authors: Letsolo, B. T., Jones, R. E., Rowson, J., Grimstead, J. W., Keith, W. N., Jenkins, G. J.S., and Baird, D. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2017 Letsolo et al.
First Published:First published in PLoS ONE 12(3):e0174833
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
573449Experimental Cancer Medicine Centre (ECMC)Thomas EvansCancer Research UK (CAN-RES-UK)15584ICS - EXPERIMENTAL THERAPEUTICS