Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer.
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10216/110357 |
Resumo: | Purpose The prognosis of gastric cancer (GC) is poor, and the molecular pathogenesis players are vastly unknown. Surgery remains the primary option in GC treatment. The aim of this study was to investigate the impact of somatic CDH1 alterations in prognosis and survival of patients with GC. Patients and Methods A series of patients with sporadic and familial GC (diffuse and intestinal; n _ 246) were analyzed for somatic CDH1 mutations, promoter hypermethylation, and loss of heterozygosity (LOH) by polymerase chain reaction sequencing. E-cadherin protein expression was determined by immunohistochemistry. Associations between molecular, clinicopathologic, and survival data were analyzed. Results CDH1 somatic alterations were found in approximately 30% of all patients with GC. Both histologic types of sporadic GC displayed LOH in 7.5%, mutations in 1.7%, and hypermethylation in 18.4% of patients. Primary tumors from hereditary diffuse GC, lacking germline CDH1 alterations, showed exclusively CDH1 promoter hypermethylation in 50% of patients. Familial intestinal GC (FIGC) tumors showed LOH in 9.4% and hypermethylation in 17.0%. CDH1 alterations did not associate with a particular pattern of E-cadherin expression. Importantly, the worst patient survival rate among all GCs analyzed was seen in patients with tumors carrying CDH1 structural alterations, preferentially those belonging to FIGC families. Conclusion CDH1 somatic alterations exist in all clinical settings and histotypes of GC and associate with different survival rates. Their screening at GC diagnosis may predict patient prognosis and is likely to improve management of patients with this disease. |
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Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer.AdultAgedCadherins/geneticsCadherins/metabolismDNA MethylationFemaleGene DeletionGene Expression Regulation NeoplasticGenetic Predisposition to DiseaseHumansImmunohistochemistryKaplan-Meier EstimateLoss of HeterozygosityMaleMiddle AgedMutationPolymerase Chain ReactionPrognosisPromoter Regions GeneticStomach Neoplasms/geneticsStomach Neoplasms/mortalityPurpose The prognosis of gastric cancer (GC) is poor, and the molecular pathogenesis players are vastly unknown. Surgery remains the primary option in GC treatment. The aim of this study was to investigate the impact of somatic CDH1 alterations in prognosis and survival of patients with GC. Patients and Methods A series of patients with sporadic and familial GC (diffuse and intestinal; n _ 246) were analyzed for somatic CDH1 mutations, promoter hypermethylation, and loss of heterozygosity (LOH) by polymerase chain reaction sequencing. E-cadherin protein expression was determined by immunohistochemistry. Associations between molecular, clinicopathologic, and survival data were analyzed. Results CDH1 somatic alterations were found in approximately 30% of all patients with GC. Both histologic types of sporadic GC displayed LOH in 7.5%, mutations in 1.7%, and hypermethylation in 18.4% of patients. Primary tumors from hereditary diffuse GC, lacking germline CDH1 alterations, showed exclusively CDH1 promoter hypermethylation in 50% of patients. Familial intestinal GC (FIGC) tumors showed LOH in 9.4% and hypermethylation in 17.0%. CDH1 alterations did not associate with a particular pattern of E-cadherin expression. Importantly, the worst patient survival rate among all GCs analyzed was seen in patients with tumors carrying CDH1 structural alterations, preferentially those belonging to FIGC families. Conclusion CDH1 somatic alterations exist in all clinical settings and histotypes of GC and associate with different survival rates. Their screening at GC diagnosis may predict patient prognosis and is likely to improve management of patients with this disease.American Society of Clinical Oncology 20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10216/110357eng0732-183X10.1200/JCO.2012.44.4612Corso, GCarvalho, JMarrelli, DVindigni, CCarvalho, BSeruca, RRoviello, FOliveira, Cinfo: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:RCAAP2023-11-29T14:42:23Zoai:repositorio-aberto.up.pt:10216/110357Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:07:11.568197Repositório 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 |
Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. |
title |
Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. |
spellingShingle |
Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. Corso, G Adult Aged Cadherins/genetics Cadherins/metabolism DNA Methylation Female Gene Deletion Gene Expression Regulation Neoplastic Genetic Predisposition to Disease Humans Immunohistochemistry Kaplan-Meier Estimate Loss of Heterozygosity Male Middle Aged Mutation Polymerase Chain Reaction Prognosis Promoter Regions Genetic Stomach Neoplasms/genetics Stomach Neoplasms/mortality |
title_short |
Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. |
title_full |
Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. |
title_fullStr |
Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. |
title_full_unstemmed |
Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. |
title_sort |
Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer. |
author |
Corso, G |
author_facet |
Corso, G Carvalho, J Marrelli, D Vindigni, C Carvalho, B Seruca, R Roviello, F Oliveira, C |
author_role |
author |
author2 |
Carvalho, J Marrelli, D Vindigni, C Carvalho, B Seruca, R Roviello, F Oliveira, C |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Corso, G Carvalho, J Marrelli, D Vindigni, C Carvalho, B Seruca, R Roviello, F Oliveira, C |
dc.subject.por.fl_str_mv |
Adult Aged Cadherins/genetics Cadherins/metabolism DNA Methylation Female Gene Deletion Gene Expression Regulation Neoplastic Genetic Predisposition to Disease Humans Immunohistochemistry Kaplan-Meier Estimate Loss of Heterozygosity Male Middle Aged Mutation Polymerase Chain Reaction Prognosis Promoter Regions Genetic Stomach Neoplasms/genetics Stomach Neoplasms/mortality |
topic |
Adult Aged Cadherins/genetics Cadherins/metabolism DNA Methylation Female Gene Deletion Gene Expression Regulation Neoplastic Genetic Predisposition to Disease Humans Immunohistochemistry Kaplan-Meier Estimate Loss of Heterozygosity Male Middle Aged Mutation Polymerase Chain Reaction Prognosis Promoter Regions Genetic Stomach Neoplasms/genetics Stomach Neoplasms/mortality |
description |
Purpose The prognosis of gastric cancer (GC) is poor, and the molecular pathogenesis players are vastly unknown. Surgery remains the primary option in GC treatment. The aim of this study was to investigate the impact of somatic CDH1 alterations in prognosis and survival of patients with GC. Patients and Methods A series of patients with sporadic and familial GC (diffuse and intestinal; n _ 246) were analyzed for somatic CDH1 mutations, promoter hypermethylation, and loss of heterozygosity (LOH) by polymerase chain reaction sequencing. E-cadherin protein expression was determined by immunohistochemistry. Associations between molecular, clinicopathologic, and survival data were analyzed. Results CDH1 somatic alterations were found in approximately 30% of all patients with GC. Both histologic types of sporadic GC displayed LOH in 7.5%, mutations in 1.7%, and hypermethylation in 18.4% of patients. Primary tumors from hereditary diffuse GC, lacking germline CDH1 alterations, showed exclusively CDH1 promoter hypermethylation in 50% of patients. Familial intestinal GC (FIGC) tumors showed LOH in 9.4% and hypermethylation in 17.0%. CDH1 alterations did not associate with a particular pattern of E-cadherin expression. Importantly, the worst patient survival rate among all GCs analyzed was seen in patients with tumors carrying CDH1 structural alterations, preferentially those belonging to FIGC families. Conclusion CDH1 somatic alterations exist in all clinical settings and histotypes of GC and associate with different survival rates. Their screening at GC diagnosis may predict patient prognosis and is likely to improve management of patients with this disease. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013 2013-01-01T00:00:00Z |
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 |
http://hdl.handle.net/10216/110357 |
url |
http://hdl.handle.net/10216/110357 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0732-183X 10.1200/JCO.2012.44.4612 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Society of Clinical Oncology |
publisher.none.fl_str_mv |
American Society of Clinical Oncology |
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) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799135997772955649 |