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Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC

BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-relate...

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Autores principales: Scarpa, Marco, Scarpa, Melania, Castagliuolo, Ignazio, Erroi, Francesca, Kotsafti, Andromachi, Basato, Silvia, Brun, Paola, D'Incà, Renata, Rugge, Massimo, Angriman, Imerio, Castoro, Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891122/
https://www.ncbi.nlm.nih.gov/pubmed/26862732
http://dx.doi.org/10.18632/oncotarget.7188
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author Scarpa, Marco
Scarpa, Melania
Castagliuolo, Ignazio
Erroi, Francesca
Kotsafti, Andromachi
Basato, Silvia
Brun, Paola
D'Incà, Renata
Rugge, Massimo
Angriman, Imerio
Castoro, Carlo
author_facet Scarpa, Marco
Scarpa, Melania
Castagliuolo, Ignazio
Erroi, Francesca
Kotsafti, Andromachi
Basato, Silvia
Brun, Paola
D'Incà, Renata
Rugge, Massimo
Angriman, Imerio
Castoro, Carlo
author_sort Scarpa, Marco
collection PubMed
description BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. RESULTS: The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. METHODS: Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. CONCLUSIONS: Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.
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spelling pubmed-48911222016-06-23 Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC Scarpa, Marco Scarpa, Melania Castagliuolo, Ignazio Erroi, Francesca Kotsafti, Andromachi Basato, Silvia Brun, Paola D'Incà, Renata Rugge, Massimo Angriman, Imerio Castoro, Carlo Oncotarget Research Paper BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. RESULTS: The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. METHODS: Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. CONCLUSIONS: Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance. Impact Journals LLC 2016-02-04 /pmc/articles/PMC4891122/ /pubmed/26862732 http://dx.doi.org/10.18632/oncotarget.7188 Text en Copyright: © 2016 Scarpa et al. http://creativecommons.org/licenses/by/2.5/ 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 credited.
spellingShingle Research Paper
Scarpa, Marco
Scarpa, Melania
Castagliuolo, Ignazio
Erroi, Francesca
Kotsafti, Andromachi
Basato, Silvia
Brun, Paola
D'Incà, Renata
Rugge, Massimo
Angriman, Imerio
Castoro, Carlo
Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC
title Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC
title_full Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC
title_fullStr Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC
title_full_unstemmed Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC
title_short Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC
title_sort aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated crc
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891122/
https://www.ncbi.nlm.nih.gov/pubmed/26862732
http://dx.doi.org/10.18632/oncotarget.7188
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