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Carcinogenesis Advance Access originally published online on June 29, 2005
Carcinogenesis 2005 26(12):2046-2049; doi:10.1093/carcin/bgi168
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Carcinogenesis vol.26 no.12 © Oxford University Press 2005; all rights reserved.

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

M. Brito *, J. Malta-Vacas, B. Carmona, C. Aires, P. Costa, A.P. Martins 1, S. Ramos 1, A.R. Conde 2 and C. Monteiro 2

Escola Superior de Tecnologia da Saúde de Lisboa, Lisboa, Portugal, 1 Serviço de Anatomia Patológica, Hospital de Santa Cruz, Lisboa, Portugal and 2 Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal

* To whom correspondence should be addressed. Tel: +351 218980400; Fax: +351 218980460; E-mail: miguel.brito{at}estesl.pt

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, analysing 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.


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Human Eukaryotic Release Factor 3a Depletion Causes Cell Cycle Arrest at G1 Phase through Inhibition of the mTOR Pathway
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[Abstract] [Full Text] [PDF]



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