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Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility

2005-12Journal article Open access
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dc.contributor.authorBrito, Miguel
dc.contributor.authorMalta-Vacas, Joana
dc.contributor.authorCarmona, Bruno
dc.contributor.authorAires, C.
dc.contributor.authorCosta, P.
dc.contributor.authorMartins, A. P.
dc.contributor.authorRamos, S.
dc.contributor.authorConde, A. R.
dc.contributor.authorMonteiro, C.
dc.date.accessioned2018-06-11T16:56:47Z
dc.date.available2018-06-11T16:56:47Z
dc.date.issued2005-12
dc.description.abstractGastric 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBrito M, Malta-Vacas J, Carmona B, Aires C, Costa P, Martins AP, et al. Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility. Carcinogenesis. 2005;26(12):2046-9.pt_PT
dc.identifier.doi10.1093/carcin/bgi168pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/8620
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherOxford University Presspt_PT
dc.relation.publisherversionhttps://academic.oup.com/carcin/article/26/12/2046/2390724pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAdenocarcinomapt_PT
dc.subjectAdenocarcinoma, Mucinouspt_PT
dc.subjectAmino acid sequencept_PT
dc.subjectDNApt_PT
dc.subjectDisease susceptibilitypt_PT
dc.subjectExonspt_PT
dc.subjectMolecular sequence datapt_PT
dc.subjectPeptide termination factorspt_PT
dc.subjectPeptidespt_PT
dc.subjectSequence homology, Amino acidpt_PT
dc.subjectStomach neoplasmspt_PT
dc.subjectTrinucleotide repeat expansionpt_PT
dc.titlePolyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibilitypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage2049pt_PT
oaire.citation.issue12pt_PT
oaire.citation.startPage2046pt_PT
oaire.citation.titleCarcinogenesispt_PT
oaire.citation.volume26pt_PT
person.familyNameBrito
person.givenNameMiguel
person.identifier.ciencia-id231F-F341-7E93
person.identifier.orcid0000-0001-6394-658X
person.identifier.ridA-7970-2016
person.identifier.scopus-author-id35224551000
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication4252d8e0-800c-4d67-8b13-0b711d860669
relation.isAuthorOfPublication.latestForDiscovery4252d8e0-800c-4d67-8b13-0b711d860669

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