CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer
Main Author: | |
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Publication Date: | 2019 |
Other Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | eng |
Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Download full: | https://hdl.handle.net/10216/136272 |
Summary: | Background: Diffuse gastric cancer (DGC) is associated with the reduction or absence of the expression of the cell adhesion protein E-cadherin (encoded by the CDH1 gene). Molecular characteristics are less well described for mixed gastric cancer (MGC). The main somatic alterations that have been described in the CDH1 gene are mutations, loss of heterozygosity (LOH) and promoter methylation. The aim was to analyze CDH1 somatic alterations in Mexican patients with diffuse and mixed gastric cancer. Methods: We searched for mutations in the CDH1 gene in tumor DNA from DGC (n = 13) and MGC (n = 7) patients by next generation sequencing (NGS). Validation of findings was performed using Sanger sequencing. LOH was analyzed using dinucleotide repeat markers surrounding the CDH1 gene, and methylation was investigated by DNA bisulfite conversion and sequencing. E-cadherin protein deficiency was analyzed by immunohistochemistry. Results: Seventeen point variants were identified by NGS, 13 of them were validated by Sanger sequencing. Only 1/13 had not been previously reported (c.-137C > A), and 12/13 were already reported as polymorphisms. Two DGC cases presented LOH at the locus 16q22.1 (13.3%). CDH1 promoter methylation was positive in (7/11) 63.6% and (4/6) 66.6% of the cases with DGC and MGC, respectively. E-cadherin protein deficiency was observed in 58.3% of DGC cases while 100% in MGC cases. Conclusions: While no pathogenic somatic mutations were found that could explain the diffuse histology of gastric cancer in DGC and MGC, methylation was the most common somatic inactivation event of the CDH1 gene, and LOH was rare. The previously unreported c.-137C > A variant modify the CDH1 gene expression since it alters the binding sites for transcription factors. |
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CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancerCDH1 mutationsDNA sequencingGastric CancerLOHMethylationBackground: Diffuse gastric cancer (DGC) is associated with the reduction or absence of the expression of the cell adhesion protein E-cadherin (encoded by the CDH1 gene). Molecular characteristics are less well described for mixed gastric cancer (MGC). The main somatic alterations that have been described in the CDH1 gene are mutations, loss of heterozygosity (LOH) and promoter methylation. The aim was to analyze CDH1 somatic alterations in Mexican patients with diffuse and mixed gastric cancer. Methods: We searched for mutations in the CDH1 gene in tumor DNA from DGC (n = 13) and MGC (n = 7) patients by next generation sequencing (NGS). Validation of findings was performed using Sanger sequencing. LOH was analyzed using dinucleotide repeat markers surrounding the CDH1 gene, and methylation was investigated by DNA bisulfite conversion and sequencing. E-cadherin protein deficiency was analyzed by immunohistochemistry. Results: Seventeen point variants were identified by NGS, 13 of them were validated by Sanger sequencing. Only 1/13 had not been previously reported (c.-137C > A), and 12/13 were already reported as polymorphisms. Two DGC cases presented LOH at the locus 16q22.1 (13.3%). CDH1 promoter methylation was positive in (7/11) 63.6% and (4/6) 66.6% of the cases with DGC and MGC, respectively. E-cadherin protein deficiency was observed in 58.3% of DGC cases while 100% in MGC cases. Conclusions: While no pathogenic somatic mutations were found that could explain the diffuse histology of gastric cancer in DGC and MGC, methylation was the most common somatic inactivation event of the CDH1 gene, and LOH was rare. The previously unreported c.-137C > A variant modify the CDH1 gene expression since it alters the binding sites for transcription factors.BMC20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/136272eng1471-240710.1186/s12885-019-5294-0Bustos-Carpinteyro, AOliveira, CSousa, AOliveira, PPinheiro, HCarvalho, JMagaña-Torres, MFlores-Miramontes, MAguilar-Lemarroy, AJave-Suárez, LPeregrina-Sandoval, JCruz-Ramos, JSánchez-López, Jinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T14:27:02Zoai:repositorio-aberto.up.pt:10216/136272Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:01:29.731360Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer |
title |
CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer |
spellingShingle |
CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer Bustos-Carpinteyro, A CDH1 mutations DNA sequencing Gastric Cancer LOH Methylation |
title_short |
CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer |
title_full |
CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer |
title_fullStr |
CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer |
title_full_unstemmed |
CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer |
title_sort |
CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer |
author |
Bustos-Carpinteyro, A |
author_facet |
Bustos-Carpinteyro, A Oliveira, C Sousa, A Oliveira, P Pinheiro, H Carvalho, J Magaña-Torres, M Flores-Miramontes, M Aguilar-Lemarroy, A Jave-Suárez, L Peregrina-Sandoval, J Cruz-Ramos, J Sánchez-López, J |
author_role |
author |
author2 |
Oliveira, C Sousa, A Oliveira, P Pinheiro, H Carvalho, J Magaña-Torres, M Flores-Miramontes, M Aguilar-Lemarroy, A Jave-Suárez, L Peregrina-Sandoval, J Cruz-Ramos, J Sánchez-López, J |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Bustos-Carpinteyro, A Oliveira, C Sousa, A Oliveira, P Pinheiro, H Carvalho, J Magaña-Torres, M Flores-Miramontes, M Aguilar-Lemarroy, A Jave-Suárez, L Peregrina-Sandoval, J Cruz-Ramos, J Sánchez-López, J |
dc.subject.por.fl_str_mv |
CDH1 mutations DNA sequencing Gastric Cancer LOH Methylation |
topic |
CDH1 mutations DNA sequencing Gastric Cancer LOH Methylation |
description |
Background: Diffuse gastric cancer (DGC) is associated with the reduction or absence of the expression of the cell adhesion protein E-cadherin (encoded by the CDH1 gene). Molecular characteristics are less well described for mixed gastric cancer (MGC). The main somatic alterations that have been described in the CDH1 gene are mutations, loss of heterozygosity (LOH) and promoter methylation. The aim was to analyze CDH1 somatic alterations in Mexican patients with diffuse and mixed gastric cancer. Methods: We searched for mutations in the CDH1 gene in tumor DNA from DGC (n = 13) and MGC (n = 7) patients by next generation sequencing (NGS). Validation of findings was performed using Sanger sequencing. LOH was analyzed using dinucleotide repeat markers surrounding the CDH1 gene, and methylation was investigated by DNA bisulfite conversion and sequencing. E-cadherin protein deficiency was analyzed by immunohistochemistry. Results: Seventeen point variants were identified by NGS, 13 of them were validated by Sanger sequencing. Only 1/13 had not been previously reported (c.-137C > A), and 12/13 were already reported as polymorphisms. Two DGC cases presented LOH at the locus 16q22.1 (13.3%). CDH1 promoter methylation was positive in (7/11) 63.6% and (4/6) 66.6% of the cases with DGC and MGC, respectively. E-cadherin protein deficiency was observed in 58.3% of DGC cases while 100% in MGC cases. Conclusions: While no pathogenic somatic mutations were found that could explain the diffuse histology of gastric cancer in DGC and MGC, methylation was the most common somatic inactivation event of the CDH1 gene, and LOH was rare. The previously unreported c.-137C > A variant modify the CDH1 gene expression since it alters the binding sites for transcription factors. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/10216/136272 |
url |
https://hdl.handle.net/10216/136272 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1471-2407 10.1186/s12885-019-5294-0 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
BMC |
publisher.none.fl_str_mv |
BMC |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799135938662629376 |