Publicação
Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility
| Resumo: | Gastric cancer remains a major cause of death in the developed countries, and a large percentage is still genetically unexplained. Because of their major role in cell survival, mutations in translation factors and altered expression of these genes have been associated with cancer development. Apart from its role in translation termination, the eukaryotic translation release factor 3 (eRF3) is involved in several critical cellular processes, such as cell cycle regulation, cytoskeleton organization, and apoptosis. The aim of this study was to evaluate eRF3/GSPT1 gene as a potential genetic susceptibility associated locus for gastric cancer, analyzing a stable GGC expansion in exon 1 encoding a polyglycine tract in the N-terminal domain of the protein. DNA was obtained from 139 patients with gastric cancer and from 100 individuals of a healthy control population. The GGC expansion was amplified by PCR and the number of repeats determined by genotyping in an automatic sequencer. There are five known alleles encoding from 8 to 12 glycines. The most common allele encodes 10 glycines. The 12-Gly allele was detected exclusively in the cancer patients (allelic frequency = 5%). Regardless of the genotype, patients with the 12-Gly allele had a 20-fold increased risk for gastric cancer. We also detected a single-base alteration in the gene (G274T) although no correlation with cancer development has been found. Thus, our results show that the GGC expansion may have a potential role in regulating eRF3/GSPT1 expression and/or changing the protein function that can lead to gastric cancer development. |
|---|---|
| Autores principais: | Brito, Miguel |
| Outros Autores: | Malta-Vacas, Joana; Carmona, Bruno; Aires, C.; Costa, P.; Martins, A. P.; Ramos, S.; Conde, A. R.; Monteiro, C. |
| Assunto: | Adenocarcinoma Adenocarcinoma, Mucinous Amino acid sequence DNA Disease susceptibility Exons Molecular sequence data Peptide termination factors Peptides Sequence homology, Amino acid Stomach neoplasms Trinucleotide repeat expansion |
| Ano: | 2005 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Instituto Politécnico de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Científico do Instituto Politécnico de Lisboa |
| _version_ | 1866887273872621568 |
|---|---|
| author | Brito, Miguel |
| author2 | Malta-Vacas, Joana Carmona, Bruno Aires, C. Costa, P. Martins, A. P. Ramos, S. Conde, A. R. Monteiro, C. |
| author2_role | author author author author author author author author |
| author_facet | Brito, Miguel Malta-Vacas, Joana Carmona, Bruno Aires, C. Costa, P. Martins, A. P. Ramos, S. Conde, A. R. Monteiro, C. |
| author_role | author |
| contributor_name_str_mv | RCIPL |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Brito, Miguel\",\"Person.identifier.orcid\":\"0000-0001-6394-658X\"},{\"Person.name\":\"Malta-Vacas, Joana\"},{\"Person.name\":\"Carmona, Bruno\"},{\"Person.name\":\"Aires, C.\"},{\"Person.name\":\"Costa, P.\"},{\"Person.name\":\"Martins, A. P.\"},{\"Person.name\":\"Ramos, S.\"},{\"Person.name\":\"Conde, A. R.\"},{\"Person.name\":\"Monteiro, C.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RCIPL |
| datacite.creators.creator.creatorName.fl_str_mv | Brito, Miguel Malta-Vacas, Joana Carmona, Bruno Aires, C. Costa, P. Martins, A. P. Ramos, S. Conde, A. R. Monteiro, C. |
| datacite.date.Accepted.fl_str_mv | 2005-12-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2018-06-11T16:56:47Z |
| datacite.date.embargoed.fl_str_mv | 2018-06-11T16:56:47Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Adenocarcinoma Adenocarcinoma, Mucinous Amino acid sequence DNA Disease susceptibility Exons Molecular sequence data Peptide termination factors Peptides Sequence homology, Amino acid Stomach neoplasms Trinucleotide repeat expansion |
| datacite.titles.title.fl_str_mv | Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility |
| dc.contributor.none.fl_str_mv | RCIPL |
| dc.creator.none.fl_str_mv | Brito, Miguel Malta-Vacas, Joana Carmona, Bruno Aires, C. Costa, P. Martins, A. P. Ramos, S. Conde, A. R. Monteiro, C. |
| dc.date.Accepted.fl_str_mv | 2005-12-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2018-06-11T16:56:47Z |
| dc.date.embargoed.fl_str_mv | 2018-06-11T16:56:47Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10400.21/8620 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Oxford University Press |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Adenocarcinoma Adenocarcinoma, Mucinous Amino acid sequence DNA Disease susceptibility Exons Molecular sequence data Peptide termination factors Peptides Sequence homology, Amino acid Stomach neoplasms Trinucleotide repeat expansion |
| dc.title.fl_str_mv | Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | Gastric cancer remains a major cause of death in the developed countries, and a large percentage is still genetically unexplained. Because of their major role in cell survival, mutations in translation factors and altered expression of these genes have been associated with cancer development. Apart from its role in translation termination, the eukaryotic translation release factor 3 (eRF3) is involved in several critical cellular processes, such as cell cycle regulation, cytoskeleton organization, and apoptosis. The aim of this study was to evaluate eRF3/GSPT1 gene as a potential genetic susceptibility associated locus for gastric cancer, analyzing a stable GGC expansion in exon 1 encoding a polyglycine tract in the N-terminal domain of the protein. DNA was obtained from 139 patients with gastric cancer and from 100 individuals of a healthy control population. The GGC expansion was amplified by PCR and the number of repeats determined by genotyping in an automatic sequencer. There are five known alleles encoding from 8 to 12 glycines. The most common allele encodes 10 glycines. The 12-Gly allele was detected exclusively in the cancer patients (allelic frequency = 5%). Regardless of the genotype, patients with the 12-Gly allele had a 20-fold increased risk for gastric cancer. We also detected a single-base alteration in the gene (G274T) although no correlation with cancer development has been found. Thus, our results show that the GGC expansion may have a potential role in regulating eRF3/GSPT1 expression and/or changing the protein function that can lead to gastric cancer development. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ipl.pt/bitstreams/b2a91b36-2c88-4d45-94bd-e1f7d9dede15/download |
| id | ripl_744aef7acf95abcbbccdcd1f11b10e2e |
| identifier.url.fl_str_mv | http://hdl.handle.net/10400.21/8620 |
| instacron_str | ipl |
| institution | Instituto Politécnico de Lisboa |
| instname_str | Instituto Politécnico de Lisboa |
| language | eng |
| network_acronym_str | ripl |
| network_name_str | Repositório Científico do Instituto Politécnico de Lisboa |
| oai_identifier_str | oai:repositorio.ipl.pt:10400.21/8620 |
| organization_str_mv | urn:organizationAcronym:ipl |
| person_str_mv | Brito, Miguel Brito, Miguel https://www.ciencia-id.pt/231F-F341-7E93 231F-F341-7E93 http://orcid.org/0000-0001-6394-658X 0000-0001-6394-658X Malta-Vacas, Joana Carmona, Bruno Aires, C. Costa, P. Martins, A. P. Ramos, S. Conde, A. R. Monteiro, C. |
| publishDate | 2005 |
| publisher.none.fl_str_mv | Oxford University Press |
| reponame_str | Repositório Científico do Instituto Politécnico de Lisboa |
| repository_id_str | urn:repositoryAcronym:ripl |
| service_str_mv | urn:repositoryAcronym:ripl |
| spelling | engOxford University Presspt_PTGastric cancer remains a major cause of death in the developed countries, and a large percentage is still genetically unexplained. Because of their major role in cell survival, mutations in translation factors and altered expression of these genes have been associated with cancer development. Apart from its role in translation termination, the eukaryotic translation release factor 3 (eRF3) is involved in several critical cellular processes, such as cell cycle regulation, cytoskeleton organization, and apoptosis. The aim of this study was to evaluate eRF3/GSPT1 gene as a potential genetic susceptibility associated locus for gastric cancer, analyzing a stable GGC expansion in exon 1 encoding a polyglycine tract in the N-terminal domain of the protein. DNA was obtained from 139 patients with gastric cancer and from 100 individuals of a healthy control population. The GGC expansion was amplified by PCR and the number of repeats determined by genotyping in an automatic sequencer. There are five known alleles encoding from 8 to 12 glycines. The most common allele encodes 10 glycines. The 12-Gly allele was detected exclusively in the cancer patients (allelic frequency = 5%). Regardless of the genotype, patients with the 12-Gly allele had a 20-fold increased risk for gastric cancer. We also detected a single-base alteration in the gene (G274T) although no correlation with cancer development has been found. Thus, our results show that the GGC expansion may have a potential role in regulating eRF3/GSPT1 expression and/or changing the protein function that can lead to gastric cancer development.application/pdfpt_PTPolyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibilityPersonalBrito, MiguelDSpacehttp://dspace.org/items/4252d8e0-800c-4d67-8b13-0b711d860669DSpacehttp://dspace.org/items/4252d8e0-800c-4d67-8b13-0b711d860669BritoMiguelCiência IDhttps://www.ciencia-id.pt231F-F341-7E93ORCIDhttp://orcid.org0000-0001-6394-658XResearcher IDhttps://www.researcherid.comA-7970-2016Scopus Author IDhttps://www.scopus.com35224551000Scopus Author IDhttps://www.scopus.com57200288349Malta-Vacas, JoanaCarmona, BrunoAires, C.Costa, P.Martins, A. P.Ramos, S.Conde, A. R.Monteiro, C.HostingInstitutionOrganizationalRCIPLe-mailmailto:rcaap@sp.ipl.ptrcaap@sp.ipl.ptDOIIsPartOf10.1093/carcin/bgi1682018-06-11T16:56:47Z2005-122005-12-01T00:00:00ZHandlehttp://hdl.handle.net/10400.21/8620http://purl.org/coar/access_right/c_abf2open accessAdenocarcinomaAdenocarcinoma, MucinousAmino acid sequenceDNADisease susceptibilityExonsMolecular sequence dataPeptide termination factorsPeptidesSequence homology, Amino acidStomach neoplasmsTrinucleotide repeat expansion123273 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal article2005-12http://creativecommons.org/licenses/by-nc-nd/4.0/http://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ipl.pt/bitstreams/b2a91b36-2c88-4d45-94bd-e1f7d9dede15/downloadCarcinogenesis261220462049 |
| spellingShingle | Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility Brito, Miguel Adenocarcinoma Adenocarcinoma, Mucinous Amino acid sequence DNA Disease susceptibility Exons Molecular sequence data Peptide termination factors Peptides Sequence homology, Amino acid Stomach neoplasms Trinucleotide repeat expansion |
| status | SINGLETON |
| subject.fl_str_mv | Adenocarcinoma Adenocarcinoma, Mucinous Amino acid sequence DNA Disease susceptibility Exons Molecular sequence data Peptide termination factors Peptides Sequence homology, Amino acid Stomach neoplasms Trinucleotide repeat expansion |
| title | Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility |
| title_full | Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility |
| title_fullStr | Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility |
| title_full_unstemmed | Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility |
| title_short | Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility |
| title_sort | Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility |
| topic | Adenocarcinoma Adenocarcinoma, Mucinous Amino acid sequence DNA Disease susceptibility Exons Molecular sequence data Peptide termination factors Peptides Sequence homology, Amino acid Stomach neoplasms Trinucleotide repeat expansion |
| topic_facet | Adenocarcinoma Adenocarcinoma, Mucinous Amino acid sequence DNA Disease susceptibility Exons Molecular sequence data Peptide termination factors Peptides Sequence homology, Amino acid Stomach neoplasms Trinucleotide repeat expansion |
| url | http://hdl.handle.net/10400.21/8620 |
| visible | 1 |