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Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients

BACKGROUND: Mismatch repair (MMR) genes are known to be frequently altered in colorectal cancer (CRC). Both genetics and epigenetics modifications seems to be relevant in this phenomenon, however it is still not clear how these two aspects are interconnected. The present study aimed at characterizin...

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Autores principales: Vymetalkova, Veronika Polakova, Slyskova, Jana, Korenkova, Vlasta, Bielik, Ludovit, Langerova, Lucie, Prochazka, Pavel, Rejhova, Alexandra, Schwarzova, Lucie, Pardini, Barbara, Naccarati, Alessio, Vodicka, Pavel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913626/
https://www.ncbi.nlm.nih.gov/pubmed/24484585
http://dx.doi.org/10.1186/1471-2350-15-17
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author Vymetalkova, Veronika Polakova
Slyskova, Jana
Korenkova, Vlasta
Bielik, Ludovit
Langerova, Lucie
Prochazka, Pavel
Rejhova, Alexandra
Schwarzova, Lucie
Pardini, Barbara
Naccarati, Alessio
Vodicka, Pavel
author_facet Vymetalkova, Veronika Polakova
Slyskova, Jana
Korenkova, Vlasta
Bielik, Ludovit
Langerova, Lucie
Prochazka, Pavel
Rejhova, Alexandra
Schwarzova, Lucie
Pardini, Barbara
Naccarati, Alessio
Vodicka, Pavel
author_sort Vymetalkova, Veronika Polakova
collection PubMed
description BACKGROUND: Mismatch repair (MMR) genes are known to be frequently altered in colorectal cancer (CRC). Both genetics and epigenetics modifications seems to be relevant in this phenomenon, however it is still not clear how these two aspects are interconnected. The present study aimed at characterizing of epigenetic and gene expression profiles of MMR genes in sporadic CRC patients from the Czech Republic, a country with one of the highest incidences of this cancer all over Europe. METHODS: Expression levels and CpG promoter methylation status of all MMR genes were evaluated in DNA from tumor and adjacent mucosal samples of 53 incident CRC patients. RESULTS: We have found significantly increased transcription levels in EXO1 gene in tumor tissues (P = 0.05) and significant over-expression of MSH3 gene in colon tumors when compared to adjacent mucosal tissues (P = 0.02). Interestingly, almost all MMR genes were differently expressed when localization of tumors was compared. In particular, colon tumors showed an up-regulation of EXO1, MSH2, MSH3, MSH6, and PMS2 genes in comparison to rectal tumors (P = 0.02). Expression levels of all MMR genes positively correlated between each other. The promoter methylation of MLH1 gene was observed in 9% of CRC tissues only. CONCLUSIONS: In our study, we have observed different pattern of MMR genes expression according to tumor localization. However, a lack of association between methylation in MMR genes and their corresponding expressions was noticed in this study, the relationship between these two aspects is worthy to be analyzed in larger population studies and in pre-malignant stages.
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spelling pubmed-39136262014-02-05 Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients Vymetalkova, Veronika Polakova Slyskova, Jana Korenkova, Vlasta Bielik, Ludovit Langerova, Lucie Prochazka, Pavel Rejhova, Alexandra Schwarzova, Lucie Pardini, Barbara Naccarati, Alessio Vodicka, Pavel BMC Med Genet Research Article BACKGROUND: Mismatch repair (MMR) genes are known to be frequently altered in colorectal cancer (CRC). Both genetics and epigenetics modifications seems to be relevant in this phenomenon, however it is still not clear how these two aspects are interconnected. The present study aimed at characterizing of epigenetic and gene expression profiles of MMR genes in sporadic CRC patients from the Czech Republic, a country with one of the highest incidences of this cancer all over Europe. METHODS: Expression levels and CpG promoter methylation status of all MMR genes were evaluated in DNA from tumor and adjacent mucosal samples of 53 incident CRC patients. RESULTS: We have found significantly increased transcription levels in EXO1 gene in tumor tissues (P = 0.05) and significant over-expression of MSH3 gene in colon tumors when compared to adjacent mucosal tissues (P = 0.02). Interestingly, almost all MMR genes were differently expressed when localization of tumors was compared. In particular, colon tumors showed an up-regulation of EXO1, MSH2, MSH3, MSH6, and PMS2 genes in comparison to rectal tumors (P = 0.02). Expression levels of all MMR genes positively correlated between each other. The promoter methylation of MLH1 gene was observed in 9% of CRC tissues only. CONCLUSIONS: In our study, we have observed different pattern of MMR genes expression according to tumor localization. However, a lack of association between methylation in MMR genes and their corresponding expressions was noticed in this study, the relationship between these two aspects is worthy to be analyzed in larger population studies and in pre-malignant stages. BioMed Central 2014-01-31 /pmc/articles/PMC3913626/ /pubmed/24484585 http://dx.doi.org/10.1186/1471-2350-15-17 Text en Copyright © 2014 Vymetalkova 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 Article
Vymetalkova, Veronika Polakova
Slyskova, Jana
Korenkova, Vlasta
Bielik, Ludovit
Langerova, Lucie
Prochazka, Pavel
Rejhova, Alexandra
Schwarzova, Lucie
Pardini, Barbara
Naccarati, Alessio
Vodicka, Pavel
Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients
title Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients
title_full Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients
title_fullStr Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients
title_full_unstemmed Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients
title_short Molecular characteristics of mismatch repair genes in sporadic colorectal tumors in Czech patients
title_sort molecular characteristics of mismatch repair genes in sporadic colorectal tumors in czech patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913626/
https://www.ncbi.nlm.nih.gov/pubmed/24484585
http://dx.doi.org/10.1186/1471-2350-15-17
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