Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. Aberrant hypermethylation in the promoter region of some known or putative tumor suppressor genes (TSGs) occurs frequently during the development of various cancers including head and neck squamous cell carcinoma (HNSCC). In this study we used an expanded mRNA expression profiling approach followed by microarray expression analysis to identify epigenetically inactivated genes in HNSCC. Two HNSCC cell lines were treated with 5-aza-2-deoxycytidine followed by microarray analysis to identify epigenetically silenced genes in HNSCC. 1960, 614, and 427 genes were upregulated in HNSCC cell lines JHU-012, JHU-011 and the combination of both cell lines, respectively. HNSCC tumor and normal mucosal samples were used for gene profiling by a 47K mRNA gene expression array and we found, 7140 genes were downregulated in HNSCC tumors compared to normal mucosa as determined by microarray analysis and were integrated with cell line data. Integrative analysis defined 126 candidate genes, of which only seven genes showed differentially methylation in tumors and no methylation in normal mucosa after bisulfite sequencing. After validation by QMSP, one gene, GNG7, was confirmed as being highly methylated in tumors and unmethylated in normal mucosal and salivary rinse samples demonstrating cancer-specific methylation in HNSCC tissues. TXNIP and TUSC2 were partially methylated in tumors and normal salivary rinses but unmethylated in normal mucosa. We concluded GNG7 as a highly specific promoter methylated gene associated with HNSCC. In addition, TXNIP and TUSC2 are also potential biomarkers for HNSCC.
Identification of guanine nucleotide-binding protein γ-7 as an epigenetically silenced gene in head and neck cancer by gene expression profiling.
Sex
View SamplesThe classical sacrococcygeal chordoma tumor presents with a typical morphology of lobulated myxoid tumor tissue with cords, strands and nests of tumor cells consisting of small non-vacuolated cells, intermediate cells with a wide range of vacuolization and large heavily vacuolated (physaliferous) cells. Because of its rare incidence, lack of suited model systems and technical limitations analysis was only performed on bulk tumor mass neglecting its heterogeneous composition. We aimed at elucidating the differences between small non-vacuolated and large physaliferous cells on the genomic and transcriptomic level. Secondly, we intended to clarify whether the observed cell types are derived from genetically distinct clones or rather represent different phenotypes. Using the chordoma cell line MUG-Chor1 we monitored morphological changes via time lapse experiments. We isolated pure fractions of each phenotype by means of laser microdissection or micromanipulation allowing phenotype-specific analysis. Pools of 100 cells each were genetically profiled after whole genome amplification by array comparative genomic hybridization. For expression analysis 20 cells each were subjected to whole transcriptom amplification, forwarded to RNA microarray analysis and qRT-PCR. Time lapse analysis unveiled small non-vacuolated cells to develop into large physaliferous cells via intermediate cells containing an increasing amount of vacuoles. Furthermore, we showed small and large physaliferous cells to proliferate at the same rate but intermediate cells to be the most proliferating cell phenotype. Small non-vacuolated and large physaliferous cells showed identical copy number variations. Despite their obvious morphological disparities we detected only modest changes in over all gene expression. However, verification of candidate genes yielded significant up-regulation of ALG11 (700-fold), PPP2CB (18.6-fold), and UCHL3 (18.7-fold) in large physaliferous cells.
Resolving tumor heterogeneity: genes involved in chordoma cell development identified by low-template analysis of morphologically distinct cells.
Cell line
View SamplesIn this study gene expression profiles for 307 cases of advanced bladder cancers were compared to molecular phenotype at the tumor cell level. TUR-B tissue for RNA extraction was macrodissected from the close vicinity of the tissue sampled for immunohistochemistry to ensure high-quality sampling and to minimize the effects of intra-tumor heterogeneity. Despite excellent agreement between gene expression values and IHC-score at the single marker level, broad differences emerge when samples are clustered at the global mRNA versus tumor cell (IHC) levels. Classification at the different levels give different results in a systematic fashion, which implicates that analysis at both levels is required for optimal subtype-classification of bladder cancer.
Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification.
Specimen part
View SamplesDynamical response to oxygen downshift under fermentation conditions was tested by taking sample before (S1) and after (S2, S3 and S4) the oxygen downshift. The dynamical changes relevant for ongoing research on physiology were applied.
Norvaline is accumulated after a down-shift of oxygen in Escherichia coli W3110.
No sample metadata fields
View SamplesWe aimed to provide a molecular description of Lynch syndrome-associated urothelial cancer in relation to molecular subtypes of sporadic bladder cancer. Whole genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was analyzed and compared with data from sporadic bladder cancer.
Molecular subtype classification of urothelial carcinoma in Lynch syndrome.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Estrogen receptor subtype beta2 is involved in neuromast development in zebrafish (Danio rerio) larvae.
No sample metadata fields
View SamplesOur overall objective is to identify key differences in gene expression signaling pathways in the epithelial and intralobular stromal compartments during prepartum mammary remodeling and development in the dry cow.
Transcriptome analysis of epithelial and stromal contributions to mammogenesis in three week prepartum cows.
No sample metadata fields
View SamplesThe role of ERbeta2 in zebrafish larvae was investigated by injection of a Morpholino against ERbeta2. After 72hpf, the morphants showed a strong disruption in their sensory systems. ERbeta2 has been shown to be needed for the normal functioning of the sensory system organs, the neuromasts. The mechanisms involved in the neuromast disruption in ERbeta2 morphants was identified by microarrays gene screening. After comparison of two screening with low and hign concentration of Morpholinos, genes that were present in the two microarrays screening were selected. The genes were then chosen by relevance for the mechanisms involved in the role of ERbeta2 in neuromast development. The ngn1 transcription factor, Notch3 and Notch1a showed to be up-regulated, also confirmed by in situ hybridization. The Notch signaling is known to be involved in cell fate in developing neuromasts. The overall conclusion is that ERbeta2 by interacting with the notch signaling pathways is critical for normal development of the neuromast of the lateral line in zebrafish.
Estrogen receptor subtype beta2 is involved in neuromast development in zebrafish (Danio rerio) larvae.
No sample metadata fields
View SamplesThe role of ERbeta2 in zebrafish larvae was investigated by injection of a Morpholino against ERbeta2. After 72hpf, the morphants showed a strong disruption in their sensory systems. ERbeta2 has been shown to be needed for the normal functioning of the sensory system organs, the neuromasts. The mechanisms involved in the neuromast disruption in ERbeta2 morphants was identified by microarrays gene screening. After comparison of two screening with low and high concentration of Morpholinos, genes that were present in the two microarrays screening were selected. The genes were then chosen by relevance for the mechanisms involved in the role of ERbeta2 in neuromast development. The ngn1 transcription factor, Notch3 and Notch1a showed to be up-regulated, also confirmed by in situ hybridization. The Notch signaling is known to be involved in cell fate in developing neuromasts. The overall conclusion is that ERbeta2 by interacting with the notch signaling pathways is critical for normal development of the neuromast of the lateral line in zebrafish.
Estrogen receptor subtype beta2 is involved in neuromast development in zebrafish (Danio rerio) larvae.
No sample metadata fields
View SamplesThe effects of 7.5 micromolar parthenolide (PTL) were assessed on primary CD34+ acute myelogenous leukemia specimens obtained from 12 patients.
Discovery of agents that eradicate leukemia stem cells using an in silico screen of public gene expression data.
No sample metadata fields
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