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Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and without Cancer in the Pancreas
A large body of evidence supports a key role for telomere dysfunction in carcinogenesis due to the induction of chromosomal instability. To study telomere shortening in precancerous pancreatic lesions, we measured telomere lengths using quantitative fluorescence in situ hybridization in the normal p...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319908/ https://www.ncbi.nlm.nih.gov/pubmed/25658358 http://dx.doi.org/10.1371/journal.pone.0117575 |
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author | Matsuda, Yoko Ishiwata, Toshiyuki Izumiyama-Shimomura, Naotaka Hamayasu, Hideki Fujiwara, Mutsunori Tomita, Ken-ichiro Hiraishi, Naoki Nakamura, Ken-ichi Ishikawa, Naoshi Aida, Junko Takubo, Kaiyo Arai, Tomio |
author_facet | Matsuda, Yoko Ishiwata, Toshiyuki Izumiyama-Shimomura, Naotaka Hamayasu, Hideki Fujiwara, Mutsunori Tomita, Ken-ichiro Hiraishi, Naoki Nakamura, Ken-ichi Ishikawa, Naoshi Aida, Junko Takubo, Kaiyo Arai, Tomio |
author_sort | Matsuda, Yoko |
collection | PubMed |
description | A large body of evidence supports a key role for telomere dysfunction in carcinogenesis due to the induction of chromosomal instability. To study telomere shortening in precancerous pancreatic lesions, we measured telomere lengths using quantitative fluorescence in situ hybridization in the normal pancreatic duct epithelium, pancreatic intraepithelial neoplasias (PanINs), and cancers. The materials employed included surgically resected pancreatic specimens without cancer (n = 33) and with invasive ductal carcinoma (n = 36), as well as control autopsy cases (n = 150). In comparison with normal ducts, telomere length was decreased in PanIN-1, −2 and −3 and cancer. Furthermore, telomeres were shorter in cancer than in PanIN-1 and −2. Telomere length in cancer was not associated with histological type, lesion location, or cancer stage. PanINs with or without cancer showed similar telomere lengths. The incidences of atypical mitosis and anaphase bridges, which are morphological characteristics of chromosomal instability, were negatively correlated with telomere length. The telomeres in normal duct epithelium became shorter with aging, and those in PanINs or cancers were shorter than in age-matched controls, suggesting that telomere shortening occurs even when histological changes are absent. Our data strongly suggest that telomere shortening occurs in the early stages of pancreatic carcinogenesis and progresses with precancerous development. Telomere shortening and chromosomal instability in the duct epithelium might be associated with carcinogenesis of the pancreas. Determination of telomere length in pancreatic ductal lesions may be valuable for accurate detection and risk assessment of pancreatic cancer. |
format | Online Article Text |
id | pubmed-4319908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43199082015-02-18 Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and without Cancer in the Pancreas Matsuda, Yoko Ishiwata, Toshiyuki Izumiyama-Shimomura, Naotaka Hamayasu, Hideki Fujiwara, Mutsunori Tomita, Ken-ichiro Hiraishi, Naoki Nakamura, Ken-ichi Ishikawa, Naoshi Aida, Junko Takubo, Kaiyo Arai, Tomio PLoS One Research Article A large body of evidence supports a key role for telomere dysfunction in carcinogenesis due to the induction of chromosomal instability. To study telomere shortening in precancerous pancreatic lesions, we measured telomere lengths using quantitative fluorescence in situ hybridization in the normal pancreatic duct epithelium, pancreatic intraepithelial neoplasias (PanINs), and cancers. The materials employed included surgically resected pancreatic specimens without cancer (n = 33) and with invasive ductal carcinoma (n = 36), as well as control autopsy cases (n = 150). In comparison with normal ducts, telomere length was decreased in PanIN-1, −2 and −3 and cancer. Furthermore, telomeres were shorter in cancer than in PanIN-1 and −2. Telomere length in cancer was not associated with histological type, lesion location, or cancer stage. PanINs with or without cancer showed similar telomere lengths. The incidences of atypical mitosis and anaphase bridges, which are morphological characteristics of chromosomal instability, were negatively correlated with telomere length. The telomeres in normal duct epithelium became shorter with aging, and those in PanINs or cancers were shorter than in age-matched controls, suggesting that telomere shortening occurs even when histological changes are absent. Our data strongly suggest that telomere shortening occurs in the early stages of pancreatic carcinogenesis and progresses with precancerous development. Telomere shortening and chromosomal instability in the duct epithelium might be associated with carcinogenesis of the pancreas. Determination of telomere length in pancreatic ductal lesions may be valuable for accurate detection and risk assessment of pancreatic cancer. Public Library of Science 2015-02-06 /pmc/articles/PMC4319908/ /pubmed/25658358 http://dx.doi.org/10.1371/journal.pone.0117575 Text en © 2015 Matsuda et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Matsuda, Yoko Ishiwata, Toshiyuki Izumiyama-Shimomura, Naotaka Hamayasu, Hideki Fujiwara, Mutsunori Tomita, Ken-ichiro Hiraishi, Naoki Nakamura, Ken-ichi Ishikawa, Naoshi Aida, Junko Takubo, Kaiyo Arai, Tomio Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and without Cancer in the Pancreas |
title | Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and without Cancer in the Pancreas |
title_full | Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and without Cancer in the Pancreas |
title_fullStr | Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and without Cancer in the Pancreas |
title_full_unstemmed | Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and without Cancer in the Pancreas |
title_short | Gradual Telomere Shortening and Increasing Chromosomal Instability among PanIN Grades and Normal Ductal Epithelia with and without Cancer in the Pancreas |
title_sort | gradual telomere shortening and increasing chromosomal instability among panin grades and normal ductal epithelia with and without cancer in the pancreas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319908/ https://www.ncbi.nlm.nih.gov/pubmed/25658358 http://dx.doi.org/10.1371/journal.pone.0117575 |
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