Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA110847 | ENA |
REPOSITORIES: ENA
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Project description:Gastric cancers frequently show chromosomal alterations which can cause activation of oncogenes, and/or inactivation of tumour suppressor genes. In gastric cancer several chromosomal regions are described to be frequently lost, but for most of the regions, no tumour suppressor genes have been identified yet. The present study aimed to identify tumour suppressor genes inactivated by nonsense mutation and deletion in gastric cancer by means of GINI (gene identification by nonsense mediated decay inhibition) and whole genome copy number analysis. Material and Methods: Two non-commercial gastric cancer cell lines, GP202 and IPA220, were transfected with siRNA directed against UPF1, to specifically inhibit the nonsense mediated decay (NMD) pathway, and with siRNA directed against non-specific siRNA duplexes (CVII) as a control. Microarray expression experiments were performed in triplicate on 4x44 K agilent arrays by hybridizing RNA from UPF1-transfected cells against non-specific CVII-transfected cells. In addition, array CGH of the two cell lines was performed on 4x44K agilent arrays to obtain the DNA copy number profiles. Mutation analysis of GINI candidates was performed by sequencing. Results: UPF1 expression was reduced for >70% and >80% in the GP202 and IPA220 gastric cancer cell lines, respectively. Integration of array CGH and microarray expression data provided a list of 134 and 50 candidate genes inactivated by nonsense mutation and deletion for GP202 and IPA220, respectively. We selected 12 candidate genes for mutation analysis. Sequence analysis was performed on 11 genes. One gene, PLA2G4A, showed a silent mutation, and in two genes, CTSA and PTPRJ, missense mutations were detected. No nonsense mutations were detected in any of the 11 genes tested. Conclusions: Although UPF1 was substantially repressed, thus resulting in the inhibition of the NMD system, we did not find genes inactivated by nonsense mutations. Our results show that the GINI strategy leads to a high number of false positives.
2009-09-19 | GSE12928 | GEO
Project description:Expression profiling was used to identify genes differentially expressed in MSS (microsatellite stable) and MSI (microsatellite unstable) colon cancer cell lines. Data submitted in support of manuscript entitled Villin expression is frequently lost in poorly differentiated colon cancer, Diego Arango, Sheren Al-Obaidi, David S. Williams, Jose Dopeso, Rocco Mazzolini, Georgia Corner, Do-Sun Byun, Carmel Murone, Lars Tögel, Nikolajs Zeps, Lauri A. Aaltonen, Barry Iacopetta and John M. Mariadason, American Journal of Pathology, 2012. 5 microsatellite stable (MSS) and 5 microsatellite unstable (MSI) colon cancer cell lines profiled. Each cell line grown and arrayed in duplicate, and the duplicates averaged for each cell line before calculating means for MSS and MSI lines.
2012-02-07 | E-GEOD-35566 | biostudies-arrayexpress
Project description:Inhibition of the nonsense mediated decay (NMD) mechanism in cells results in stabilization of transcripts carrying premature translation termination codons. A strategy referred to as gene indentification by NMD inhibition (GINI) has been proposed to identify genes carrying nonsense mutations (Noensie & Dietz, 2001). Genes containing frameshift mutations in colon cancer cell line have been identifying mutatnt genes using GINI, we have now further improved the strategy. In this approach, inhibition of NMD with emetine is complemented with inhibiting NMD by blocking the phosphorylation of the hUpf1 protein with caffeine. In addition, to enhance the GINI strategy, comparing mRNA level alterations produced by inhibiting transcription alone or inhbiiting transcription together with NMD following caffeine pretreatment were used for the efficient identification of false positives produced as a result of stress response to NMD inhibition. To demonstrate the improved efficiency of this approach, we analyzed colon cancer cell lines showing microstellite instability. Bi-allelic inactivating mutations were found in the FXR1, SEC1L1, NCOR1, BAT3, PHD14, ZNF294, C190ORF5 genes as well as genes coding for proteins with yet unknown functions. Keywords: microarray, gene expression, Affymetrix, drug treatment, emetine, caffeine, actinomycin D, novel tumor suppressor gene candidates
2006-08-11 | GSE5486 | GEO
Project description:DNA methylation is a key contributor to normal mammalian development, although, abnormal CpG islands methylation has been described to have a role in carcinogenesis. In gastric cancer, it is observed a global hypomethylation within the bulk genome and local hypermethylation at specific tumor suppressor genes. Conversely, the absence of DNA methylation may be an important step in stable transcriptional activation of oncogenes, contributing to tumor development. The screening of genes modulated by DNA methylation in gastric cancer may contribute to the identification of tumor suppressor genes and/or oncogenes modulated by DNA methylation never described in this neoplasia. In this experiment we aimed to identify differentially expressed genes by comparing 5-Aza-2’-deoxycytidine (5-AZAdC)-treated and non-treated gastric cancer cell lines. 5-AZAdC is a demethylation agent and has received FDA approval for the treatment of myelodysplastic syndromes. This drug has also showed capacity to treat solid tumors with low dose. The ACP02 and ACP03 gastric cancer cell lines used in this experiment were previously established by our research group from primary gastric adenocarcinomas classified as diffuse and intestinal types, respectively. Both cell lines present chromosome 8 trisomy, MYC amplification, and TP53 loss of copy. Moreover, ACP03 is able to start a tumorigenesis process in Cebus apellas.
2019-04-30 | E-MTAB-7880 | biostudies-arrayexpress
Project description:Gastric cancer is the second most common cause of cancer death worldwide, but incidence and mortality rates show large variations across different countries. Variation in risk factors between different populations, including environmental and host factors influencing gastric cancer risk, have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We set out to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA). DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis. Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p<0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p=0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK patients and Caucasian SA patients and between native and Caucasian SA patients. In conclusion, gastric cancers from South African and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms underlying the disease. 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients.
2011-06-27 | E-GEOD-22789 | biostudies-arrayexpress
Project description:Two major genetic pathways leading to colorectal carcinoma can well be distinguished; the ‘suppressor pathway’, which is characterized by inactivation of tumor-suppressor genes and the ‘mutator pathway’, which is characterized by microsatellite instability. The purpose of this study is to explore a third putative pathway; microsatellite and chromosome stable colorectal cancer where an alternative cancer-causative mechanism might play a role.
| 2021019 | ecrin-mdr-crc
Project description:Inhibition of the nonsense mediated decay (NMD) mechanism in cells results in stabilization of transcripts carrying premature translation termination codons. A strategy referred to as gene indentification by NMD inhibition (GINI) has been proposed to identify genes carrying nonsense mutations (Noensie & Dietz, 2001). Genes containing frameshift mutations in colon cancer cell line have been identifying mutatnt genes using GINI, we have now further improved the strategy. In this approach, inhibition of NMD with emetine is complemented with inhibiting NMD by blocking the phosphorylation of the hUpf1 protein with caffeine. In addition, to enhance the GINI strategy, comparing mRNA level alterations produced by inhibiting transcription alone or inhbiiting transcription together with NMD following caffeine pretreatment were used for the efficient identification of false positives produced as a result of stress response to NMD inhibition. To demonstrate the improved efficiency of this approach, we analyzed colon cancer cell lines showing microstellite instability. Bi-allelic inactivating mutations were found in the FXR1, SEC1L1, NCOR1, BAT3, PHD14, ZNF294, C190ORF5 genes as well as genes coding for proteins with yet unknown functions. Experiment Overall Design: Using GINI2 as a method of identifying novel biallelic truncating mutations in MSI+ colon cancer cells, various treatment conditions were applied to cultured colon cancer cell lines LS180 (MSI+) and SW480 (MSI-) and gene expression profiling was measured using Affymetrix GeneChip U133 Plus 2 arrays.
2008-06-13 | E-GEOD-5486 | biostudies-arrayexpress
Project description:Expression profiling was used to identify genes differentially expressed in MSS (microsatellite stable) and MSI (microsatellite unstable) colon cancer cell lines. Data submitted in support of manuscript entitled Villin expression is frequently lost in poorly differentiated colon cancer, Diego Arango, Sheren Al-Obaidi, David S. Williams, Jose Dopeso, Rocco Mazzolini, Georgia Corner, Do-Sun Byun, Carmel Murone, Lars Tögel, Nikolajs Zeps, Lauri A. Aaltonen, Barry Iacopetta and John M. Mariadason, American Journal of Pathology, 2012.
2012-02-07 | GSE35566 | GEO
Project description:Identification of potential tumor suppressor genes using the GINI strategy in Mantle Cell Lymphoma cell lines Experiment Overall Design: Inhibition of the NMD pathway was performed in Mantle Cell Lymphoma cell lines according to a modified protocol previously described (Noensie EN et al Nat Biotechnol 2001;19:434-439; Huusko P et al, Nat Gentet 2004; 36:979-983). The cells were treated with emetine or with emetine followed by incubation with actinomycin D during a time course. Mock treated cells were used as reference.
2008-06-15 | E-GEOD-6728 | biostudies-arrayexpress
Project description:Transcriptional profiling of comparing control and GAPLINC stable knocking-down human gastric cancer cell lines. Goal was to determine the different gene expression between control and GAPLINC stable knocking-down human gastric cancer cell lines. Control and GAPLINC stable knocking-down human gastric cancer cell lines were prepared for RNA extraction and hybridization on Affymetrix microarrays.
2014-08-19 | E-GEOD-51651 | biostudies-arrayexpress