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Genetic and Epigenetic Alterations of CDH1 Regulatory Regions in Hereditary and Sporadic Gastric Cancer

E-cadherin is a key player in gastric cancer (GC) and germline alterations of CDH1, its encoding gene, are responsible for Hereditary Diffuse Gastric Cancer (HDGC) syndrome. This study aimed at elucidating the role of genetic variants and DNA methylation of CDH1 promoter and enhancers in the regulat...

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Autores principales: Tedaldi, Gianluca, Molinari, Chiara, São José, Celina, Barbosa-Matos, Rita, André, Ana, Danesi, Rita, Arcangeli, Valentina, Ravegnani, Mila, Saragoni, Luca, Morgagni, Paolo, Rebuzzi, Francesca, Canale, Matteo, Pignatta, Sara, Ferracci, Elisa, Martinelli, Giovanni, Ranzani, Guglielmina Nadia, Oliveira, Carla, Calistri, Daniele, Ulivi, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151134/
https://www.ncbi.nlm.nih.gov/pubmed/34066170
http://dx.doi.org/10.3390/ph14050457
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author Tedaldi, Gianluca
Molinari, Chiara
São José, Celina
Barbosa-Matos, Rita
André, Ana
Danesi, Rita
Arcangeli, Valentina
Ravegnani, Mila
Saragoni, Luca
Morgagni, Paolo
Rebuzzi, Francesca
Canale, Matteo
Pignatta, Sara
Ferracci, Elisa
Martinelli, Giovanni
Ranzani, Guglielmina Nadia
Oliveira, Carla
Calistri, Daniele
Ulivi, Paola
author_facet Tedaldi, Gianluca
Molinari, Chiara
São José, Celina
Barbosa-Matos, Rita
André, Ana
Danesi, Rita
Arcangeli, Valentina
Ravegnani, Mila
Saragoni, Luca
Morgagni, Paolo
Rebuzzi, Francesca
Canale, Matteo
Pignatta, Sara
Ferracci, Elisa
Martinelli, Giovanni
Ranzani, Guglielmina Nadia
Oliveira, Carla
Calistri, Daniele
Ulivi, Paola
author_sort Tedaldi, Gianluca
collection PubMed
description E-cadherin is a key player in gastric cancer (GC) and germline alterations of CDH1, its encoding gene, are responsible for Hereditary Diffuse Gastric Cancer (HDGC) syndrome. This study aimed at elucidating the role of genetic variants and DNA methylation of CDH1 promoter and enhancers in the regulation of gene expression. For this purpose, we analyzed genetic variants of the CDH1 gene through Next-Generation Sequencing (NGS) in a series of GC cell lines (NCI-N87, KATO-III, SNU-1, SNU-5, GK2, AKG, KKP) and the corresponding CDH1 expression levels. By bisulfite genomic sequencing, we analyzed the methylation status of CDH1 regulatory regions in 8 GC cell lines, in a series of 13 sporadic GC tissues and in a group of 20 HDGC CDH1-negative patients and 6 healthy controls. The NGS analysis on CDH1 coding and regulatory regions detected genetic alterations in 3 out of 5 GC cell lines lacking functional E-cadherin. CDH1 regulatory regions showed different methylation patterns in patients and controls, GC cell lines and GC tissues, expressing different E-cadherin levels. Our results showed that alterations in terms of genetic variants and DNA methylation patterns of both promoter and enhancers are associated with CDH1 expression levels and have a role in its regulation.
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spelling pubmed-81511342021-05-27 Genetic and Epigenetic Alterations of CDH1 Regulatory Regions in Hereditary and Sporadic Gastric Cancer Tedaldi, Gianluca Molinari, Chiara São José, Celina Barbosa-Matos, Rita André, Ana Danesi, Rita Arcangeli, Valentina Ravegnani, Mila Saragoni, Luca Morgagni, Paolo Rebuzzi, Francesca Canale, Matteo Pignatta, Sara Ferracci, Elisa Martinelli, Giovanni Ranzani, Guglielmina Nadia Oliveira, Carla Calistri, Daniele Ulivi, Paola Pharmaceuticals (Basel) Article E-cadherin is a key player in gastric cancer (GC) and germline alterations of CDH1, its encoding gene, are responsible for Hereditary Diffuse Gastric Cancer (HDGC) syndrome. This study aimed at elucidating the role of genetic variants and DNA methylation of CDH1 promoter and enhancers in the regulation of gene expression. For this purpose, we analyzed genetic variants of the CDH1 gene through Next-Generation Sequencing (NGS) in a series of GC cell lines (NCI-N87, KATO-III, SNU-1, SNU-5, GK2, AKG, KKP) and the corresponding CDH1 expression levels. By bisulfite genomic sequencing, we analyzed the methylation status of CDH1 regulatory regions in 8 GC cell lines, in a series of 13 sporadic GC tissues and in a group of 20 HDGC CDH1-negative patients and 6 healthy controls. The NGS analysis on CDH1 coding and regulatory regions detected genetic alterations in 3 out of 5 GC cell lines lacking functional E-cadherin. CDH1 regulatory regions showed different methylation patterns in patients and controls, GC cell lines and GC tissues, expressing different E-cadherin levels. Our results showed that alterations in terms of genetic variants and DNA methylation patterns of both promoter and enhancers are associated with CDH1 expression levels and have a role in its regulation. MDPI 2021-05-12 /pmc/articles/PMC8151134/ /pubmed/34066170 http://dx.doi.org/10.3390/ph14050457 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tedaldi, Gianluca
Molinari, Chiara
São José, Celina
Barbosa-Matos, Rita
André, Ana
Danesi, Rita
Arcangeli, Valentina
Ravegnani, Mila
Saragoni, Luca
Morgagni, Paolo
Rebuzzi, Francesca
Canale, Matteo
Pignatta, Sara
Ferracci, Elisa
Martinelli, Giovanni
Ranzani, Guglielmina Nadia
Oliveira, Carla
Calistri, Daniele
Ulivi, Paola
Genetic and Epigenetic Alterations of CDH1 Regulatory Regions in Hereditary and Sporadic Gastric Cancer
title Genetic and Epigenetic Alterations of CDH1 Regulatory Regions in Hereditary and Sporadic Gastric Cancer
title_full Genetic and Epigenetic Alterations of CDH1 Regulatory Regions in Hereditary and Sporadic Gastric Cancer
title_fullStr Genetic and Epigenetic Alterations of CDH1 Regulatory Regions in Hereditary and Sporadic Gastric Cancer
title_full_unstemmed Genetic and Epigenetic Alterations of CDH1 Regulatory Regions in Hereditary and Sporadic Gastric Cancer
title_short Genetic and Epigenetic Alterations of CDH1 Regulatory Regions in Hereditary and Sporadic Gastric Cancer
title_sort genetic and epigenetic alterations of cdh1 regulatory regions in hereditary and sporadic gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151134/
https://www.ncbi.nlm.nih.gov/pubmed/34066170
http://dx.doi.org/10.3390/ph14050457
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