Genetic and Epigenetic Alterations of <i>CDH1</i> Regulatory Regions in Hereditary and Sporadic Gastric Cancer
E-cadherin is a key player in gastric cancer (GC) and germline alterations of <i>CDH1</i>, 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 <i>CDH1</i>...
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MDPI AG
2021-05-01
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| Online Access: | https://www.mdpi.com/1424-8247/14/5/457 |
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| author | Gianluca Tedaldi Chiara Molinari Celina São José Rita Barbosa-Matos Ana André Rita Danesi Valentina Arcangeli Mila Ravegnani Luca Saragoni Paolo Morgagni Francesca Rebuzzi Matteo Canale Sara Pignatta Elisa Ferracci Giovanni Martinelli Guglielmina Nadia Ranzani Carla Oliveira Daniele Calistri Paola Ulivi |
| author_facet | Gianluca Tedaldi Chiara Molinari Celina São José Rita Barbosa-Matos Ana André Rita Danesi Valentina Arcangeli Mila Ravegnani Luca Saragoni Paolo Morgagni Francesca Rebuzzi Matteo Canale Sara Pignatta Elisa Ferracci Giovanni Martinelli Guglielmina Nadia Ranzani Carla Oliveira Daniele Calistri Paola Ulivi |
| author_sort | Gianluca Tedaldi |
| collection | DOAJ |
| description | E-cadherin is a key player in gastric cancer (GC) and germline alterations of <i>CDH1</i>, 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 <i>CDH1</i> promoter and enhancers in the regulation of gene expression. For this purpose, we analyzed genetic variants of the <i>CDH1</i> 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 <i>CDH1</i> expression levels. By bisulfite genomic sequencing, we analyzed the methylation status of <i>CDH1</i> regulatory regions in 8 GC cell lines, in a series of 13 sporadic GC tissues and in a group of 20 HDGC <i>CDH1</i>-negative patients and 6 healthy controls. The NGS analysis on <i>CDH1</i> coding and regulatory regions detected genetic alterations in 3 out of 5 GC cell lines lacking functional E-cadherin. <i>CDH1</i> 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 <i>CDH1</i> expression levels and have a role in its regulation. |
| first_indexed | 2024-03-10T11:28:56Z |
| format | Article |
| id | doaj.art-93314491ddb043b1bf1a47a691c33b20 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T11:28:56Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-93314491ddb043b1bf1a47a691c33b202023-11-21T19:24:56ZengMDPI AGPharmaceuticals1424-82472021-05-0114545710.3390/ph14050457Genetic and Epigenetic Alterations of <i>CDH1</i> Regulatory Regions in Hereditary and Sporadic Gastric CancerGianluca Tedaldi0Chiara Molinari1Celina São José2Rita Barbosa-Matos3Ana André4Rita Danesi5Valentina Arcangeli6Mila Ravegnani7Luca Saragoni8Paolo Morgagni9Francesca Rebuzzi10Matteo Canale11Sara Pignatta12Elisa Ferracci13Giovanni Martinelli14Guglielmina Nadia Ranzani15Carla Oliveira16Daniele Calistri17Paola Ulivi18Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italyi3S, Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugali3S, Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugali3S, Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, PortugalRomagna Cancer Registry, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyRomagna Cancer Registry, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyRomagna Cancer Registry, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyPathology Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, ItalyDepartment of General Surgery, Morgagni-Pierantoni Hospital, 47121 Forlì, ItalyBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyLaboratory of Stem Cells and Cancer Genomics, University of Trento, 38123 Trento, ItalyDepartment of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyDepartment of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italyi3S, Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, PortugalBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyBiosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, ItalyE-cadherin is a key player in gastric cancer (GC) and germline alterations of <i>CDH1</i>, 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 <i>CDH1</i> promoter and enhancers in the regulation of gene expression. For this purpose, we analyzed genetic variants of the <i>CDH1</i> 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 <i>CDH1</i> expression levels. By bisulfite genomic sequencing, we analyzed the methylation status of <i>CDH1</i> regulatory regions in 8 GC cell lines, in a series of 13 sporadic GC tissues and in a group of 20 HDGC <i>CDH1</i>-negative patients and 6 healthy controls. The NGS analysis on <i>CDH1</i> coding and regulatory regions detected genetic alterations in 3 out of 5 GC cell lines lacking functional E-cadherin. <i>CDH1</i> 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 <i>CDH1</i> expression levels and have a role in its regulation.https://www.mdpi.com/1424-8247/14/5/457gastric cancer<i>CDH1</i> geneDNA methylationregulatory regionsgenetic predispositionNext-Generation Sequencing |
| spellingShingle | Gianluca Tedaldi Chiara Molinari Celina São José Rita Barbosa-Matos Ana André Rita Danesi Valentina Arcangeli Mila Ravegnani Luca Saragoni Paolo Morgagni Francesca Rebuzzi Matteo Canale Sara Pignatta Elisa Ferracci Giovanni Martinelli Guglielmina Nadia Ranzani Carla Oliveira Daniele Calistri Paola Ulivi Genetic and Epigenetic Alterations of <i>CDH1</i> Regulatory Regions in Hereditary and Sporadic Gastric Cancer Pharmaceuticals gastric cancer <i>CDH1</i> gene DNA methylation regulatory regions genetic predisposition Next-Generation Sequencing |
| title | Genetic and Epigenetic Alterations of <i>CDH1</i> Regulatory Regions in Hereditary and Sporadic Gastric Cancer |
| title_full | Genetic and Epigenetic Alterations of <i>CDH1</i> Regulatory Regions in Hereditary and Sporadic Gastric Cancer |
| title_fullStr | Genetic and Epigenetic Alterations of <i>CDH1</i> Regulatory Regions in Hereditary and Sporadic Gastric Cancer |
| title_full_unstemmed | Genetic and Epigenetic Alterations of <i>CDH1</i> Regulatory Regions in Hereditary and Sporadic Gastric Cancer |
| title_short | Genetic and Epigenetic Alterations of <i>CDH1</i> Regulatory Regions in Hereditary and Sporadic Gastric Cancer |
| title_sort | genetic and epigenetic alterations of i cdh1 i regulatory regions in hereditary and sporadic gastric cancer |
| topic | gastric cancer <i>CDH1</i> gene DNA methylation regulatory regions genetic predisposition Next-Generation Sequencing |
| url | https://www.mdpi.com/1424-8247/14/5/457 |
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