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

Brito, Miguel; Malta-Vacas, Joana; Carmona, Bruno; Aires, César Augusto Martins; Costa, Patrícia Godoy Garcia; Martins, Ana Paula; Ramos, Sância; Conde, A. R.; Monteiro, Carolino

doi:10.1093/carcin/bgi168

Cited by 38 publications

(34 citation statements)

References 30 publications

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“…Such variation could influence seizure thresholds or contribute to other disorders. Polymorphic glycine repeats have previously been associated with disease (Brito et al, 2005;Werner et al, 2006), hence further analysis of the correlation between the number of glycine residues and HCN1 function is warranted.…”

Section: Discussionmentioning

confidence: 99%

Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy

Tang

Sander

Craven

et al. 2008

Neurobiology of Disease

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Hyperpolarization-activated cyclic nucleotide-gated (HCN1-4) channels play an important role in the regulation of neuronal rhythmicity. In the present study we describe the mutation analysis of HCN1 and HCN2 in 84 unrelated patients with idiopathic generalized epilepsy (IGE). Several functional variants were identified including the amino acid substitution R527Q in HCN2 exon 5. HCN2 channels containing the R527Q variant demonstrated a trend towards a decreased slope of the conductance-voltage relation. We also identified a variant in the splice donor site of HCN2 exon 5 that results in the formation of a cryptic splice donor. In HCN1, the amino acid substitution A881T was identified in one sporadic IGE patient but was not observed in 510 controls. Seven variants were examined further in a case-control association study consisting of a larger cohort of IGE patients. Further studies are warranted to more clearly establish the contribution of HCN1 and HCN2 dysfunction to the genetic variance of common IGE syndromes.

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Section: Discussionmentioning

confidence: 99%

Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy

Tang

Sander

Craven

et al. 2008

Neurobiology of Disease

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“…Our data showed increased expression of cell adhesion genes, such as CTNNB1, PXN and CDH13, and were correlated with increased invasion and metastasis. Cell cycle control-related genes, such as GSPT1 and CKS1, were also found to be involved in invasion and metastasis of malignant tumor (Huerta et al, 2003;Brito et al, 2005). Our findings suggest that GSPT1 and CKS1 were upregulated in GC9811-P cells, which may contribute to peritoneal invasive or metastatic processes in gastric adenocarcinoma.…”

Section: Discussionmentioning

confidence: 49%

Screening and identification of peritoneal metastasis-related genes of gastric adenocarcinoma using a cDNA microarray

Bai¹,

Wang²,

Wang³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. With the aim of identifying peritoneal metastasis-related genes in gastric cancer, we performed a broad analysis of differential gene expression between the parental cell line GC9811 and its highly metastatic peritoneal counterpart, cell line GC9811-P. Two fluorescent cDNA probes, labeled with Cy3 and Cy5 dyes, were prepared from GC9811 and GC9811-P mRNA samples by the reverse transcription method. The two color probes were then mixed and hybridized to a cDNA chip constructed with double-dots from 11,901 human genes; this was scanned at two wavelengths. The experiment was repeated twice. In GC9811-P cells, 218 genes were upregulated and 30 genes were downregulated compared with the parental cell lines. Some selected genes were confirmed by RT-PCR and Western blot; we found that S100A4 and CTNNB1 were upregulated Genes in peritoneal metastasis of gastric cancer and PTEN was downregulated in GC9811-P cells. Identification of these differentially expressed genes could contribute to disclose the molecular mechanisms involved and provide new targets for therapeutic intervention to avoid peritoneal dissemination of gastric adenocarcinoma.

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“…The most discriminatory, distinctive influence for UICC stage II comes from the gene GTP-binding elongation factor GSPT2, also known as eRF3b, that is involved in cell cycle regulation. 21 A possible involvement in pancreatic cancer 22 and an association with gastric cancer susceptibility 23 suggest a role of the eRF3 family in tumor development. The transcription factor HOXA9 had the most pronounced discriminatory, distinctive upregulation in UICC stage III patients.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional census of 36 microdissected colorectal cancers yields a gene signature to distinguish UICC II and III

Groene

Mansmann

Meister

et al. 2006

Intl Journal of Cancer

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UICC stage II and III colorectal cancers (CRC) differ fundamentally in prognosis and therapeutic concepts. To analyze differential gene expression between both stages and to establish a relationship between molecular background and clinical presentation, tumor material from 36 unselected consecutive patients presenting with sporadic CRC, 18 UICC stage II and 18 UICC stage III, were laser microdissected to separate epithelial tumor cells. Gene expression levels were measured using U133A Affymetrix gene arrays. Twelve CRC associated signal transduction pathways as well as all 22,000 probe sets were screened for differential gene expression. We identified a signature consisting of 45 probe sets that allowed discrimination between UICC stage II and stage III with a rate of correct classification of about 80%. The most distinctive elements in this signature were the gene GSTP-binding elongation factor (GSPT2) and the transcription factor HOXA9. Differential expression of these genes was confirmed by quantitative real-time polymerase chain reaction (p (HOXA9) 5 0.04, p (GSTP2) 5 0.02). Despite the reliability of the presented data, there was no substantial differential expression of genes in cancer-related pathways. However, the comparison with recently published data corroborates the 45 gene signature showing structural agreement in the direction of fold changes of gene expression levels for our set of genes chosen to discriminate between both stages. ' 2006 Wiley-Liss, Inc.Key words: colorectal cancer; gene expression analysis; gene signature; classification; UICC stage II; UICC stage III In colorectal cancer (CRC), the prognosis and the type of adjuvant treatment is highly dependent upon the stage of disease. The current staging of CRC is predominantly based on clinical and pathological parameters such as local tumor extension, lymph node involvement and distant metastases. 1,2 More than 70% of patients with curative resection of CRC are classified as UICC stage II and III. While UICC stage II CRC is generally considered to be local and less aggressive with 5-year recurrence rates of 20-25%, tumors of stage UICC III are more dynamic by spreading metastases to lymph nodes. This results in a 5-year recurrence rate of more than 40% after radical resection 3 and constitutes the reason for recommendation of adjuvant therapy.

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

Cited by 38 publications

References 30 publications

Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy

Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy

Screening and identification of peritoneal metastasis-related genes of gastric adenocarcinoma using a cDNA microarray

Transcriptional census of 36 microdissected colorectal cancers yields a gene signature to distinguish UICC II and III

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