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Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium

ABSTRACT: Barrett’s esophagus (BE) is an asymptomatic, pre-malignant condition of the esophagus that can progress to esophageal adenocarcinoma (EAC). BE arises typically in individuals with long-standing gastroesophageal reflux disease (GERD). The neoplastic progression of BE has been extensively st...

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Autores principales: Bajpai, Manisha, Aviv, Hana, Das, Kiron M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564717/
https://www.ncbi.nlm.nih.gov/pubmed/23194200
http://dx.doi.org/10.1186/1755-8166-5-43
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author Bajpai, Manisha
Aviv, Hana
Das, Kiron M
author_facet Bajpai, Manisha
Aviv, Hana
Das, Kiron M
author_sort Bajpai, Manisha
collection PubMed
description ABSTRACT: Barrett’s esophagus (BE) is an asymptomatic, pre-malignant condition of the esophagus that can progress to esophageal adenocarcinoma (EAC). BE arises typically in individuals with long-standing gastroesophageal reflux disease (GERD). The neoplastic progression of BE has been extensively studied histologically and defined as a metaplasia- dyplasia- carcinoma sequence. However the genetic basis of this process is poorly understood. It is conceived that preclinical models of BE may facilitate discovery of molecular markers due to ease of longitudinal sampling. Clinical markers to stratify the patients at higher risk are vital to institute appropriate therapeutic intervention since EAC has very poor prognosis. We developed a dynamic in-vitro BE carcinogenesis (BEC) model by exposing naïve Barrett’s epithelium cell line (BAR-T) to acid and bile at pH4 (B4), 5min/day for a year. The BEC model acquired malignant characteristics after chronic repeated exposure to B4 similar to the sequential progression of BE to EAC in vivo. AIM: To study cytogenetic changes during progressive transformation in the BEC model. RESULTS: We observed that the BAR-T cells progressively acquired several chromosomal abnormalities in the BEC model. Evidence of chromosomal loss (-Y) rearrangements [t(10;16) and dup (11q)] and clonal selection appeared during the early stages of the BEC model. Clonal selection resulted in a stabilized monoclonal population of cells that had a changed morphology and formed colony in soft agar. BAR-T cells grown in parallel without any exposure did not show any of these abnormalities. CONCLUSIONS: Prolonged acid and bile exposure induced chromosomal aberrations and clonal selection in benign BAR-T cells. Since aneuploidy preceded morphological/dysplastic changes in the BEC model, chromosomal aberrations may be an early predictor of BE progression. The [t(10;16) and dup(11q)] aberrations identified in this study harbor several genes associated with cancer and may be responsible for neoplastic behavior of cells. After further validation, in-vivo, they may be clinically useful for diagnosis of BE, progressing to dysplasia/esophageal adenocarcinoma.
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spelling pubmed-35647172013-02-08 Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium Bajpai, Manisha Aviv, Hana Das, Kiron M Mol Cytogenet Research ABSTRACT: Barrett’s esophagus (BE) is an asymptomatic, pre-malignant condition of the esophagus that can progress to esophageal adenocarcinoma (EAC). BE arises typically in individuals with long-standing gastroesophageal reflux disease (GERD). The neoplastic progression of BE has been extensively studied histologically and defined as a metaplasia- dyplasia- carcinoma sequence. However the genetic basis of this process is poorly understood. It is conceived that preclinical models of BE may facilitate discovery of molecular markers due to ease of longitudinal sampling. Clinical markers to stratify the patients at higher risk are vital to institute appropriate therapeutic intervention since EAC has very poor prognosis. We developed a dynamic in-vitro BE carcinogenesis (BEC) model by exposing naïve Barrett’s epithelium cell line (BAR-T) to acid and bile at pH4 (B4), 5min/day for a year. The BEC model acquired malignant characteristics after chronic repeated exposure to B4 similar to the sequential progression of BE to EAC in vivo. AIM: To study cytogenetic changes during progressive transformation in the BEC model. RESULTS: We observed that the BAR-T cells progressively acquired several chromosomal abnormalities in the BEC model. Evidence of chromosomal loss (-Y) rearrangements [t(10;16) and dup (11q)] and clonal selection appeared during the early stages of the BEC model. Clonal selection resulted in a stabilized monoclonal population of cells that had a changed morphology and formed colony in soft agar. BAR-T cells grown in parallel without any exposure did not show any of these abnormalities. CONCLUSIONS: Prolonged acid and bile exposure induced chromosomal aberrations and clonal selection in benign BAR-T cells. Since aneuploidy preceded morphological/dysplastic changes in the BEC model, chromosomal aberrations may be an early predictor of BE progression. The [t(10;16) and dup(11q)] aberrations identified in this study harbor several genes associated with cancer and may be responsible for neoplastic behavior of cells. After further validation, in-vivo, they may be clinically useful for diagnosis of BE, progressing to dysplasia/esophageal adenocarcinoma. BioMed Central 2012-11-29 /pmc/articles/PMC3564717/ /pubmed/23194200 http://dx.doi.org/10.1186/1755-8166-5-43 Text en Copyright ©2012 Bajpai et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Bajpai, Manisha
Aviv, Hana
Das, Kiron M
Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium
title Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium
title_full Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium
title_fullStr Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium
title_full_unstemmed Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium
title_short Prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign Barrett’s epithelium
title_sort prolonged exposure to acid and bile induces chromosome abnormalities that precede malignant transformation of benign barrett’s epithelium
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564717/
https://www.ncbi.nlm.nih.gov/pubmed/23194200
http://dx.doi.org/10.1186/1755-8166-5-43
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