EYA4 is a non-small cell lung cancer tumor suppressor located in the susceptibility locus on chromosome 6q
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Ian Wilson
PROVIDER: E-GEOD-19034 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This study was undertaken to identify novel tumour suppressor genes in lung adenocarcinoma. EYA4, located at 6q23.2 was identified as a frequently lost and hypermethylated gene in the analyzed samples. 7 Breast cancer cell lines profiled on the SMRTr array in conjunction with matched DNA methylation data, allelic status and gene expression data for integrative analysis.
2010-12-31 | E-GEOD-21540 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE17768: An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: gene expression GSE17769: An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: DNA methylation GSE21347: An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: allelic status GSE21540: An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer: CGH Refer to individual Series
2010-12-31 | E-GEOD-21541 | biostudies-arrayexpress
Project description:Within the complex wheat flour proteome, the gluten proteins have attracted most of the attention because of their importance in determining the functional properties of wheat flour doughs and their roles in human health conditions such as celiac disease and food allergies. However, certain non-gluten proteins also trigger immunological responses but may be present in flour in low amounts or obscured by the more abundant gluten proteins in two-dimensional gels of total protein preparations. Non-gluten proteins were preferentially extracted from the flour with a dilute salt solution and separated by two-dimensional gel electrophoresis. Proteins in 172 gel spots were identified by tandem mass spectrometry after cleavage with trypsin or chymotrypsin. Fifty-seven different types of non-gluten proteins were identified, including 14 types that are known or suspected immunogenic proteins. The predominant proteins in 18 gel spots were gluten proteins. Transgenic wheat lines in which specific groups of gluten proteins were suppressed by RNA interference were used to estimate the amount of carry-over of gluten proteins in the salt-soluble protein fraction. Analysis of salt-soluble proteins from a transgenic line missing omega-1,2 gliadins demonstrated that certain omega-1,2 gliadins were present in large amounts in the salt-soluble fraction and obscured relatively small amounts of beta-amylase and protein disulfide isomerase. In comparison, analysis of a transgenic line in which alpha gliadins were absent revealed that glyceraldehyde-3 phosphate dehydrogenase was a moderately abundant protein that co-migrated with several alpha gliadins. The proteomic map of the non-gluten protein fraction of wheat flour developed in this study complements a proteomic map of the total flour proteins developed previously for the same cultivar. Knowing the identities of low abundance proteins in the flour as well as proteins that are hidden by some of the major gluten proteins on two-dimensional gels is critical for studies aimed at assessing the immunogenic potential of wheat flour and determining how the growth conditions of the plants affect the levels of specific immunogenic proteins in the flour.
2020-08-17 | PXD017260 | Pride
Project description:We carried out a genome-wide cfDNA methylation profiling study of pancreatic ductal adenocarcinoma (PDAC) patients by Methylated DNA Immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Compared with healthy individuals, 775 differentially methylated regions (DMRs) located in promoter regions were identified in PDAC patients with 761 hypermethylated and 14 hypomethylated regions; meanwhile, 761 DMRs in CpG islands (CGIs) were identified in PDAC patients with 734 hypermethylated and 27 hypomethylated regions (p-value < 35 0.0001). 143 hypermethylated DMRs were further selected which were located in promoter regions and completely overlapped with CGIs. A total of 8 probes from 8 genes were found to fairly distinguish PDAC patients from the healthy individuals, including TRIM73, FAM150A, EPB41L3, SIX3, MIR663, MAPT, LOC100128977 and LOC100130148.
2020-10-29 | E-MTAB-9678 | biostudies-arrayexpress
Project description:BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is usually incurable. Contrary to genetic mechanisms involved in PDAC pathogenesis, epigenetic alterations are ill defined. Here we determine the contribution of epigenetically silenced genes to the development of PDAC. METHODS: We investigated methylated DNAs from PDACs, chronic pancreatitis and normal pancreatic tissues using Methyl-CpG immunoprecipitation followed by microarray hybridization. Promoter methylation of selected genes was confirmed with the Epityper assay. Expression levels were evaluated by quantitative RT-PCR. WNK2 was further investigated in tissue microarrays, methylation analysis of early pancreatic intraepithelial neoplasia (PanINs), mouse models for PDAC and pancreatitis, re-expression studies after demethylation, and cell growth assays using WNK2 overexpression. RESULTS: A total of 3.8% of 27.800 interrogated CpG islands were hypermethylated in PDAC versus normal and chronic pancreatitis tissues. Hypermethylation was confirmed in 12 out of 13 selected islands and was associated with gene silencing in 4 of them. The most prominently hypermethylated gene, WNK2, was further investigated. Demethylation assays confirmed the link between methylation and expression. WNK2 hypermethylation was higher in pancreatic tumor cells than in surrounding inflamed tissues and was observed in PanIN lesions as well as in a PDAC mouse model. WNK2 mRNA and protein expression were lower in PDAC and chronic pancreatitis compared to normal tissues both in patients and mouse models. Overexpression of WNK2 led to a reduced cell growth and WNK2 expression in tissues correlated negatively with the expression of pERK1/2, a downstream target of WNK2 responsible for cell proliferation. CONCLUSIONS: WNK2 is downregulated by promoter hypermethylation early in PDAC pathogenesis and may support tumor cell growth via the ERK-MAPK pathway. 3 types of pancreatic tissue samples: 5 normals, 2 chronic pancreatitis, 7 tumors (PDAC)
2012-11-01 | E-GEOD-37480 | biostudies-arrayexpress
Project description:The moss Physcomitrella patens is remarkable for the ease with which mutant alleles of any gene can be generated by highly efficient homologous recombination-mediated gene targeting. Targeted transgene integration is believed to be mediated through the capture of transforming DNA by the homologous recombination DNA repair pathway. To identify components of this pathway in P. patens we have undertaken a transcriptomic analysis of the response to the sublethal induction of bleomycin-induced DNA double-strand breaks using massively parallel (Illumina) cDNA sequencing. Transcripts significantly increased in bleomycin-treated tissue include a number encoding conserved DNA-DSB components in both the homology-dependent pathway (including Rad51, CTiP, DNA ligase 1, Replication protein A, ATR) and the non-homologous end-joining pathway (including Xrcc4, DNA ligase 4, Ku70, Ku80, PARP). Differentially regulated cell-cycle components include up-regulated Rad9 and Hus1 DNA-damage-related checkpoint proteins and down-regulated D-type cyclins and B-type CDKs, commensurate with the imposition of a checkpoint in the G2 stage of the cell cycle characteristic of homology-dependent DNA-DSB repair. Comparison of the DNA damage transcriptome of P. patens with that of A. thaliana reveals significant up-regulation of a number of P. patens genes encoding ATP-dependent chromatin remodelling helicases of the SNF-2 class. These represent candidates for investigation of their role in mediating efficient gene targeting in P. patens. Gene expression profiling monitored by transcript abundance in control tissue and tissue treated with the DNA-DSB inducing agent, bleomycin
2010-11-10 | E-GEOD-25237 | biostudies-arrayexpress
Project description:Alcohol is a major risk factor for hepatocellular carcinoma (HCC) although the mechanisms underlying the alcohol-related liver carcinogenesis are still poorly understood. Alcohol is known to increase hepatocarcinogenesis possibly by inducing aberrant DNA methylation through the reduced provision of methyl groups within the hepatic one-carbon metabolism. Whether the epigenetically-regulated pathways in alcohol-associated HCC can be reversible or modifiable by nutritional factors is unknown. The aim of the present study was to investigate the genome wide promoter DNA methylation profiles along with array-based, gene expression profiles in non-viral, alcohol-associated HCC. From eight HCC patients the methylation status and transcriptional levels of all annotated genes were compared by analyzing HCC tissue and the cancer-free surrounding liver tissue, following curative surgery. After merging both the DNA methylation and gene expression data, we identified 159 hypermethylated-repressed, 30 hypomethylated-induced, 49 hypermethylated-induced and 56 hypomethylated-repressed genes. A number of potentially novel candidate tumor-suppressor genes (FAM107A, IGFALS, MT1G, MT1H, RNF180) demonstrated promoter hypermethylation and transcriptional repression in alcohol-associated HCC. Notably, promoter DNA methylation appeared as the regulatory mechanism for the transcriptional repression of genes controlling the retinol metabolic pathway (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22, RDH16) and SHMT1, a key gene within one-carbon metabolism. A genome-wide DNA methylation approach linked up with array-based gene expression profiles allowed identifying a number of novel, epigenetically-regulated candidate tumor-suppressor genes in alcohol-associated hepatocarcinogenesis. Retinol metabolism genes and SHMT1 are also epigenetically-regulated through promoter DNA methylation in alcohol-associated hepatocarcinogenesis. 16 samples (8 control samples from non-neoplastic liver tissue, 8 test samples from hepatocellular carcinoma) from 8 patients affected from hepatocellular carcinoma were analyzed.
2015-05-05 | E-GEOD-59260 | biostudies-arrayexpress
Project description:Epigenetic modifications, such as aberrant DNA promoter methylation is frequently observed in cervical cancer. Identification of hypermethylated regions maybe useful for discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3) or worse may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions were characterised using genome-wide methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methyl-DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium resulting in the identification of hypermethylated differentially methylated regions (DMRs). Validation of 9 selected DMRs by MSP or BSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was applied exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples (p<0.001). Clinical validation of both markers in cervical scrapings from patients referred with an abnormal cervical smear, confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion (p<0.001) and the ROC analysis was discriminative (p<0.005). These possible methylation markers represent COL25A1 and KATNAL2 promoters and their observed increased methylation upon progression is in agreement with their biological function (cytoskeleton regulation). In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and could be potential biomarkers for early detection. Epigenetic modifications, such as aberrant DNA promoter methylation is frequently observed in cervical cancer. Identification of hypermethylated regions maybe useful for discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3) or worse may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions were characterised using genome-wide methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methyl-DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium resulting in the identification of hypermethylated differentially methylated regions (DMRs). Validation of 9 selected DMRs by MSP or BSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was applied exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples (p<0.001). Clinical validation of both markers in cervical scrapings from patients referred with an abnormal cervical smear, confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion (p<0.001) and the ROC analysis was discriminative (p<0.005). These possible methylation markers represent COL25A1 and KATNAL2 promoters and their observed increased methylation upon progression is in agreement with their biological function (cytoskeleton regulation). In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and could be potential biomarkers for early detection. MeDIP with subsequent microarray analysis was performed on DNA isolated from frozen macrodissected epithelial tissue of CIN3 lesions (n=15) and normal cervices (n=10).
2012-11-01 | E-GEOD-36319 | biostudies-arrayexpress
Project description:We evaluated the presence of genome-wide epigenetic differences at 385,000 loci using Encode HG18 DNA methylation arrays in 5 non-tumor-associated (NTA) and 4 histologically undistinguished tumor-associated (TA) prostate tissues. We identified 615 probes to be differentially methylated (p<0.05) in TA prostate, with 537 (87%) hypomethylated and 78 (13%) hypermethylated. comparison of methylation in NTA to TA prostate tissue
2012-06-27 | E-GEOD-38982 | biostudies-arrayexpress
Project description:Laminopathies are caused by mutations in components of the nuclear envelope (NE). While most NE components are widely expressed, laminopathies affect only a subset of tissues. However, the understanding of the molecular mechanisms that explain this phenomenon is still elusive. Here we have performed a genome wide DamID analysis in adult C. elegans nematodes comparing the DNA association profile of two components of the NE, Lamin/LMN-1 and Emerin/EMR-1. Although both proteins were associated to silent DNA, EMR-1 showed a predominant role in the anchoring of muscle and neuronal promoters to the nuclear periphery. Deletion of either EMR-1 or LEM-2, another integral NE protein, caused local changes in nuclear architecture with both increased and decreased LMN-1 association. Comparison of Dam::LMN-1 and Dam::EMR-1 DNA assotiation in wild type strains and Dam::LMN-1 DNA association in wild type, lem-2(tm1582) and emr-1(gk119) mutant backgrounds.
2013-12-02 | E-GEOD-44188 | biostudies-arrayexpress