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Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology

Barrett's oesophagus is a premalignant condition whose incidence is rising dramatically. Molecular markers are urgently needed to identify Barrett's patients at the highest risk of cancer progression. To this end, we have used a rapid molecular technique, restriction site mutation (RSM), t...

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Autores principales: Jenkins, G J S, Doak, S H, Griffiths, A P, Tofazzal, N, Shah, V, Baxter, J N, Parry, J M
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747568/
https://www.ncbi.nlm.nih.gov/pubmed/12698195
http://dx.doi.org/10.1038/sj.bjc.6600891
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author Jenkins, G J S
Doak, S H
Griffiths, A P
Tofazzal, N
Shah, V
Baxter, J N
Parry, J M
author_facet Jenkins, G J S
Doak, S H
Griffiths, A P
Tofazzal, N
Shah, V
Baxter, J N
Parry, J M
author_sort Jenkins, G J S
collection PubMed
description Barrett's oesophagus is a premalignant condition whose incidence is rising dramatically. Molecular markers are urgently needed to identify Barrett's patients at the highest risk of cancer progression. To this end, we have used a rapid molecular technique, restriction site mutation (RSM), to detect low-frequency mutations in the p53 tumour suppressor gene in premalignant Barrett's tissues of cancer-free patients. In total, 38 endoscopically diagnosed Barrett's patients with a range of histological stages of Barrett's progression, plus four control patients without Barrett's oesophagus, were analysed for early p53 mutations. Tissue samples taken from these patients (93 samples in total) were analysed for the presence of low-frequency p53 mutations at hotspot codons: 175, 213, 248, 249, 282. In total, 13 of the 38 Barrett's patients were shown to possess a p53 mutation in at least one sample (no mutations in the four control patients). Although no statistically significant associations were found, p53 mutations reflected histological progression in Barrett's patients with p53 mutations found in 30% of metaplasia patients (P=0.4) and low-grade dysplasia patients (P=0.33) and 45% of high-grade dysplasia patients (P=0.15). Detected p53 mutations were mainly GC to AT transitions at CpG sites.
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spelling pubmed-27475682009-09-21 Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology Jenkins, G J S Doak, S H Griffiths, A P Tofazzal, N Shah, V Baxter, J N Parry, J M Br J Cancer Genetics and Genomics Barrett's oesophagus is a premalignant condition whose incidence is rising dramatically. Molecular markers are urgently needed to identify Barrett's patients at the highest risk of cancer progression. To this end, we have used a rapid molecular technique, restriction site mutation (RSM), to detect low-frequency mutations in the p53 tumour suppressor gene in premalignant Barrett's tissues of cancer-free patients. In total, 38 endoscopically diagnosed Barrett's patients with a range of histological stages of Barrett's progression, plus four control patients without Barrett's oesophagus, were analysed for early p53 mutations. Tissue samples taken from these patients (93 samples in total) were analysed for the presence of low-frequency p53 mutations at hotspot codons: 175, 213, 248, 249, 282. In total, 13 of the 38 Barrett's patients were shown to possess a p53 mutation in at least one sample (no mutations in the four control patients). Although no statistically significant associations were found, p53 mutations reflected histological progression in Barrett's patients with p53 mutations found in 30% of metaplasia patients (P=0.4) and low-grade dysplasia patients (P=0.33) and 45% of high-grade dysplasia patients (P=0.15). Detected p53 mutations were mainly GC to AT transitions at CpG sites. Nature Publishing Group 2003-04-22 2003-04-15 /pmc/articles/PMC2747568/ /pubmed/12698195 http://dx.doi.org/10.1038/sj.bjc.6600891 Text en Copyright © 2003 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Genetics and Genomics
Jenkins, G J S
Doak, S H
Griffiths, A P
Tofazzal, N
Shah, V
Baxter, J N
Parry, J M
Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology
title Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology
title_full Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology
title_fullStr Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology
title_full_unstemmed Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology
title_short Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology
title_sort early p53 mutations in nondysplastic barrett's tissue detected by the restriction site mutation (rsm) methodology
topic Genetics and Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747568/
https://www.ncbi.nlm.nih.gov/pubmed/12698195
http://dx.doi.org/10.1038/sj.bjc.6600891
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