Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia.
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 th...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0174833&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850133467288829952 |
|---|---|
| author | Boitelo T Letsolo Rhiannon E Jones Jan Rowson Julia W Grimstead W Nicol Keith Gareth J S Jenkins Duncan M Baird |
| author_facet | Boitelo T Letsolo Rhiannon E Jones Jan Rowson Julia W Grimstead W Nicol Keith Gareth J S Jenkins Duncan M Baird |
| author_sort | Boitelo T Letsolo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d8f9b80fd6ea4b6196df8cda58935a64 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d8f9b80fd6ea4b6196df8cda58935a642025-08-20T02:31:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01123e017483310.1371/journal.pone.0174833Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia.Boitelo T LetsoloRhiannon E JonesJan RowsonJulia W GrimsteadW Nicol KeithGareth J S JenkinsDuncan M BairdBarrett'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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0174833&type=printable |
| spellingShingle | Boitelo T Letsolo Rhiannon E Jones Jan Rowson Julia W Grimstead W Nicol Keith Gareth J S Jenkins Duncan M Baird Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia. PLoS ONE |
| title | Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia. |
| title_full | Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia. |
| title_fullStr | Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia. |
| title_full_unstemmed | Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia. |
| title_short | Extensive telomere erosion is consistent with localised clonal expansions in Barrett's metaplasia. |
| title_sort | extensive telomere erosion is consistent with localised clonal expansions in barrett s metaplasia |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0174833&type=printable |
| work_keys_str_mv | AT boitelotletsolo extensivetelomereerosionisconsistentwithlocalisedclonalexpansionsinbarrettsmetaplasia AT rhiannonejones extensivetelomereerosionisconsistentwithlocalisedclonalexpansionsinbarrettsmetaplasia AT janrowson extensivetelomereerosionisconsistentwithlocalisedclonalexpansionsinbarrettsmetaplasia AT juliawgrimstead extensivetelomereerosionisconsistentwithlocalisedclonalexpansionsinbarrettsmetaplasia AT wnicolkeith extensivetelomereerosionisconsistentwithlocalisedclonalexpansionsinbarrettsmetaplasia AT garethjsjenkins extensivetelomereerosionisconsistentwithlocalisedclonalexpansionsinbarrettsmetaplasia AT duncanmbaird extensivetelomereerosionisconsistentwithlocalisedclonalexpansionsinbarrettsmetaplasia |