scholarly journals Differential gene expression profiling in human brain tumors

2001 ◽  
Vol 5 (1) ◽  
pp. 21-33 ◽  
Author(s):  
JAMES M. MARKERT ◽  
CATHERINE M. FULLER ◽  
G. YANCEY GILLESPIE ◽  
JAMES K. BUBIEN ◽  
LEE ANNE McLEAN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Solute Transport ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Cell Biology ◽  
Glutamate Transporter ◽  
Tissue Samples ◽  
Altered Expression ◽  
Primary Glioblastoma ◽  
Normal Tissues

Gene expression profiling of three human temporal lobe brain tissue samples (normal) and four primary glioblastoma multiforme (GBM) tumors using oligonucleotide microarrays was done. Moreover, confirmation of altered expression was performed by whole cell patch clamp, immunohistochemical staining, and RT-PCR. Our results identified several ion and solute transport-related genes, such as N-methyl-d-aspartate (NMDA) receptors, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 receptors, GABAA receptor subunits α3, β1, β2, and β3, the glutamate transporter, the glutamate/aspartate transporter II, the potassium channel KV2.1, hKVβ3, and the sodium/proton exchanger 1 (NHE-1), that are all downregulated in the tumors compared with the normal tissues. In contrast, aquaporin-1, possibly aquaporins-3 and -5, and GLUT-3 message appeared upregulated in the tumors. Our results also confirmed previous work showing that osteopontin, nicotinamide N-methyltransferase, murine double minute 2 (MDM2), and epithelin (granulin) are upregulated in GBMs. We also demonstrate for the first time that the cytokine and p53 binding protein, macrophage migration inhibitory factor (MIF), appears upregulated in GBMs. These results indicate that the modulation of ion and solute transport genes and heretofore unsuspected cytokines (i.e., MIF) may have profound implications for brain tumor cell biology and thus may identify potential useful therapeutic targets in GBMs.

scholarly journals Evidence for Selective Transformation of Autoreactive Immature Plasma Cells in Mice Deficient in Fasl

2004 ◽  
Vol 200 (11) ◽  
pp. 1467-1478 ◽  
Author(s):  
Jian Qiao Zhang ◽  
Cheryl Okumura ◽  
Thomas McCarty ◽  
Min Sun Shin ◽  
Partha Mukhopadhyay ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Gene Repertoire ◽  
Altered Expression ◽  
Autoreactive B Cells ◽  
Systemic Autoimmunity ◽  
The Relationship

Germline mutations in Fas and Fasl induce nonmalignant T cell hyperplasia and systemic autoimmunity and also greatly increase the risk of B cell neoplasms. B lymphomas occurring in Fasl mutant (gld) mice usually are immunoglobulin (Ig) isotype switched, secrete Ig, and are plasmacytoid in appearance but lack Myc translocations characteristic of other plasma cell (PC) neoplasms. Here, we explore the relationship between B cell autoreactivity and transformation and use gene expression profiling to further classify gld plasmacytoid lymphomas (PLs) and to identify genes of potential importance in transformation. We found that the majority of PLs derive from antigen-experienced autoreactive B cells producing antinuclear antibody or rheumatoid factor and exhibit the skewed Ig V gene repertoire and Ig gene rearrangement patterns associated with these specificities. Gene expression profiling revealed that both primary and transplanted PLs share a transcriptional profile that places them at an early stage in PC differentiation and distinguishes them from other B cell neoplasms. In addition, genes were identified whose altered expression might be relevant in lymphomagenesis. Our findings provide a strong case for targeted transformation of autoreactive B cells in gld mice and establish a valuable model for understanding the relationship between systemic autoimmunity and B cell neoplasia.

Review Paper: Gene Expression Profiling in Veterinary and Human Medicine: Overview of Applications and Proposed Quality Control Practices

2009 ◽  
Vol 46 (4) ◽  
pp. 598-603 ◽  
Author(s):  
E. J. Kort ◽  
P. Norton ◽  
P. Haak ◽  
B. Berghuis ◽  
S. Ramirez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quality Control ◽  
Quality Assurance ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Clinical Care ◽  
Lessons Learned ◽  
Reproducible Research ◽  
Tissue Samples ◽  
Wide Range

High throughput molecular analysis of veterinary tissue samples is being applied to a wide range of research questions aimed at improving survival, development of diagnostic assays, and improving the economics of commercial production of animal products. Many of these efforts also, implicitly or explicitly, have ramifications for the clinical care of humans and, potentially, animals. Here we provide an overview of applications of gene expression profiling in veterinary research and practice. We then focus on the current state of quality control and quality assurance efforts in gene expression profiling studies, underscoring lessons learned from such analysis of human samples. Finally, we propose practices aimed at ensuring the reliability and reproducibility of such assays. The implementation of quality assurance practices by a trained pathologist is an essential link in the chain of events leading ultimately to reliable and reproducible research findings and appropriate clinical care.

scholarly journals Arrays of Arrays for High-Throughput Gene Expression Profiling

2001 ◽  
Vol 11 (7) ◽  
pp. 1256-1261
Author(s):  
Patrick P. Zarrinkar ◽  
James K. Mainquist ◽  
Matthew Zamora ◽  
David Stern ◽  
John B. Welsh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Ovarian Tissue ◽  
Disease Diagnosis ◽  
Full Potential ◽  
Ovarian Carcinomas ◽  
Single Experiment ◽  
Tissue Samples

Gene expression profiling using DNA arrays is rapidly becoming an essential tool for research and drug discovery and may soon play a central role in disease diagnosis. Although it is possible to make significant discoveries on the basis of a relatively small number of expression profiles, the full potential of this technology is best realized through more extensive collections of expression measurements. The generation of large numbers of expression profiles can be a time-consuming and labor-intensive process with current one-at-a-time technology. We have developed the ability to obtain expression profiles in a highly parallel yet straightforward format using glass wafers that contain 49 individual high-density oligonucleotide arrays. This arrays of arrays concept is generalizable and can be adapted readily to other types of arrays, including spotted cDNA microarrays. It is also scalable for use with hundreds and even thousands of smaller arrays on a single piece of glass. Using the arrays of arrays approach and parallel preparation of hybridization samples in 96-well plates, we were able to determine the patterns of gene expression in 27 ovarian carcinomas and 4 normal ovarian tissue samples, along with a number of control samples, in a single experiment. This new approach significantly increases the ease, efficiency, and throughput of microarray-based experiments and makes possible new applications of expression profiling that are currently impractical.

scholarly journals Gene expression profiling of human breast tissue samples using SAGE-Seq

2010 ◽  
Vol 20 (12) ◽  
pp. 1730-1739 ◽  
Author(s):  
Z. J. Wu ◽  
C. A. Meyer ◽  
S. Choudhury ◽  
M. Shipitsin ◽  
R. Maruyama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Breast Tissue ◽  
Human Breast ◽  
Human Breast Tissue ◽  
Tissue Samples

scholarly journals Gene expression profiling in insulinomas of Men1 β-cell mutant mice reveals early genetic and epigenetic events involved in pancreatic β-cell tumorigenesis

2006 ◽  
Vol 13 (4) ◽  
pp. 1223-1236 ◽  
Author(s):  
S Fontanière ◽  
J Tost ◽  
A Wierinckx ◽  
J Lachuer ◽  
J Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Mutant Mice ◽  
Differentially Methylated Region ◽  
Β Cells ◽  
Β Cell ◽  
Cell Mutant ◽  
Altered Expression ◽  
Cyclin A2

Mutations of the MEN1 gene lead to the occurrence of multiple endocrine neoplasia type 1 (MEN1). To gain insights into the mechanisms of the tumorigenesis related to MEN1 inactivation, we have used mice in which the Men1 gene was specifically disrupted in pancreatic β-cells. In these mice, we observed full penetrance of insulinoma with defined histological characteristics of tumorigenesis. To identify the genetic factors taking part in the tumour development, we performed gene expression profiling analysis of these insulinomas at different stages. Here, we show that in late stage insulinomas, 56 genes are up-regulated and 194 are down-regulated more than fourfold compared with normal pancreatic islets. Clustering analysis reveals the deregulation of Hox gene family and the genes involved in cell proliferation and cell cycle control. The altered expression of Igf2, Igfbp3 and Igfbp6 as well as cyclin A2, B2 and D2 are confirmed by quantitative RT-PCR, with the overexpression of all the three cyclins found in early stage insulinomas. Moreover, an increased proportion of cyclin A2- and D2-expressing cells and the overexpression of insulin-like growth factor 2 (IGF2) protein are detected in mouse Men1 insulinomas by immunostaining. Interestingly, the analysis of DNA methylation patterns by quantitative serial pyrosequencing reveals that four specific CpGs in the intragenic differentially methylated region 2 (DMR2) region of the Igf2 gene known to augment transcription through methylation are significantly hypermethylated in insulinomas of Men1 β-cell mutant mice at 6 and 10 months of age, even before IGF2 overexpression can be detected. Thus, our data indicate the involvement of both genetic and epigenetic mechanisms in early tumorigenesis of β-cells related to MEN1 inactivation.

scholarly journals The Utility of Gene Expression Profiling from Tissue Samples to Support Drug Safety Assessments

ILAR Journal ◽  
2017 ◽  
Vol 58 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Daniel P. Stiehl ◽  
Elaine Tritto ◽  
Salah-Dine Chibout ◽  
André Cordier ◽  
Pierre Moulin
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Drug Safety ◽  
Expression Profiling ◽  
Tissue Samples ◽  
Safety Assessments

scholarly journals Whole-Genome Gene Expression Profiling of Formalin-Fixed, Paraffin-Embedded Tissue Samples

PLoS ONE ◽  
2009 ◽  
Vol 4 (12) ◽  
pp. e8162 ◽  
Author(s):  
Craig April ◽  
Brandy Klotzle ◽  
Thomas Royce ◽  
Eliza Wickham-Garcia ◽  
Tanya Boyaniwsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Whole Genome ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed

Comprehensive gene expression analysis of IDH1/2 mutant biliary cancers (BC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4598-4598
Author(s):  
Francesca Battaglin ◽  
Joanne Xiu ◽  
Yasmine Baca ◽  
Jia Zeng ◽  
Anthony Frank Shields ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Response ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Molecular Profile ◽  
Specific Gene ◽  
Altered Expression ◽  
Idh Mutations

4598 Background: Isocitrate dehydrogenases (IDH) mutations (mut) identify a distinct subtype of BC that has yet to be fully characterized. We recently showed that IDH1/2 mutant (mIDH) BC harbor specific gene alterations involving chromatin remodeling and DNA repair, and a differential immune markers profile compared to other mIDH GI tumors. Here we aim to further dissect the molecular profile of mIDH BC through a comprehensive gene expression profiling analysis. Methods: 524 BC samples (303 intrahepatic cholangiocarcinoma, IHCC, 67 extrahepatic cholangiocarcinoma, EHCC, 141 gallbladder, 13 unspecified) collected between February to December of 2019 were included. Samples were analyzed using NextGen DNA sequencing (NextSeq, 592 gene panel), whole transcriptome RNA sequencing (NovaSeq) and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). EBseq was used to identify differentially expressed genes in mIDH vs wild type (WT) tumors with control for FDR ( Q < 0.2). Pathway and functional enrichment analysis was performed using g:Profiler and Enrichr. Results: mIDH frequency in our cohort was 11.4% (60/524), with higher prevalence of IDH1 mut (8.8%). IHCC showed the highest mut prevalence: IDH1 13.5%, IDH2 4.6%. mIDH was more common in females ( P = 0.0036). A total of 774 genes were significantly differentially expressed between mIDH and WT: 582 underexpressed (Fold change, FC: 0.025~0.699); 192 overexpressed (FC: 1.43~3.3). Pathway enrichment showed a significant decrease of gene expression in cytokine-cytokine receptor interaction ( Q = 0.002) and inflammatory response genes ( Q = 0.005) in mIDH. Interferon-γ- and PD1 signaling-related genes expression was significantly lower in mIDH vs WT ( Q = 0.02) including IFNG (FC 0.32), NKG7 (FC 0.36), CD8B (FC 0.37), BATF (FC 0.40), PD1 (FC 0.53), SLAMF6 (FC 0.55) and PD-L2 (FC 0.60). Wnt and cadherin signaling were also enriched for altered expression in several genes in mIDH BC ( Q = 3.86e-7 and < 0.00001, respectively). Conclusions: To our knowledge, this is the largest and most extensive gene expression profiling study focused on mIDH BC. Our data show for the first time a distinct gene expression profile characterizing mIDH tumors which display significant downregulation of inflammatory response pathways and immune-related genes. These findings contribute to further the understanding of mIDH BC and may inform the future development of rational combination therapies.

scholarly journals Gene expression profiling: identification of genes with altered expression in Ayu17-449 knockout mice

2011 ◽  
Vol 10 (3) ◽  
pp. 1533-1544 ◽  
Author(s):  
Y. Li ◽  
T.T. Huang ◽  
H. Tang ◽  
K.I. Yamamura ◽  
X.Y. Pu
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Knockout Mice ◽  
Expression Profiling ◽  
Altered Expression
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