Chromosomal Aberration Patterns of Aggressive B-Cell Lymphomas Closely Correlate with Molecularly Defined Disease Subtypes and Regional mRNA Expression. An Analysis of 213 Tumor Samples within the German MMML Network.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2025-2025
Author(s):  
Swen Wessendorf
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Chromosomal Aberrations ◽  
Molecular Mechanisms ◽  
Prognostic Information ◽  
Expression Levels ◽  
Chromosome Arm ◽  
Mrna Gene ◽  
Mrna Gene Expression ◽  
Gene Expression Levels

Recently, it has been demonstrated that aggressive B-cell non-Hodgkin lymphomas (B-NHL) split up into distinct subgroups such as molecular Burkitt (mBL) and molecular non-Burkitt lymphomas (non-mBL). The non-mBL group can further be devided in activated B-cell (ABC) and germinal center B-cell (GCB) like lymphomas. In the present investigation we aimed at unravelling correlations of single or multiple chromosomal imbalances, their respective regional mRNA gene expression levels and the above mentioned molecular subgroups. Aggressive B-NHL samples (n=255) were investigated within the German network project Molecular Mechanisms in Malignant Lymphomas (MMML). Data from genomic arrayCGH analysis were evaluable for 213 lymphoma cases. Consensus review diagnoses according to WHO criteria were: DLBCL (n=154), atypical BL (n=20), typical BL (n=15) and other aggressive B-NHL (n=24). For all cases gene expression analysis was done using the Affymetrix U133A GeneChip. FISH data were available for translocations involving the MYC locus and for t(14;18). Using arrayCGH, chromosomal gains in more than 10% of all cases have been identified on 18q(24.4%), 3q(19.8%), 1q(19.1%), 12q(16.7%) 2p(16.3 %), 7p and 7q(16.3%), 6p(13.2%) and 11q(12.5%). Deletions occurred most frequently on chromosome arm 6q(20.3%), 17p(15.4%), 9p(14.8%) and 8p(10%). Molecular BLs had significantly less chromosomal aberrations than non-mBLs but frequently show gains of chromosome arm 1q. Non-mBLs show higher genomic complexity and strikingly differing aberration patterns for GCB (more than 20% gains on 1q, 2p, 7q, 11q, 12q) and ABC (more than 20% gains on 3q, 9p, 18q, loss on 6q) type lymphomas. These findings were also supported by results of genomic clustering algorithms such as non negative matrix factorization. For a large number of recurrent chromosomal aberrations we were able to delineate minimal aberrant chromosomal regions and to correlate respective regional mRNA gene expression levels. Strong proportional correlations were found for gains of 18q21.1-q21.33 and losses of 6q21-q24.3. In conclusion, genomic aberration patterns closely correlate with distinct molecular subtypes of aggressive B-NHL. These aberration patterns might serve as surrogate markers providing diagnostic and prognostic information as well as a basis for targeted gene investigations and risk adapted therapy studies.

Effects of the floor type on the gene expression of Hspa1a and cytokines in Holstein dairy cows

2019 ◽  
Author(s):  
Abdulkerim DÝLER
Keyword(s):  
Gene Expression ◽  
Positive Impact ◽  
Gene Expressions ◽  
Expression Levels ◽  
Udder Health ◽  
Rubber Mat ◽  
Mrna Gene ◽  
Tnf Gene ◽  
Mrna Gene Expression ◽  
Gene Expression Levels

This study was carried out to identify the HSPA1A, TNF, IL1B and IL6 mRNA gene expression levels of Holstein dairy cattle sheltered in different floor types. Nineteen Holstein cows were used in this study. The cattle taken into research were divided into two groups as concrete (CON; n= 10) or rubber mat (RUB; n=9). HSPA1A, TNF, IL1B and IL6 mRNA genes are isolated from milk somatic cells and the gene expression is identified by Real-Time PCR. Between the groups, the HSPA1A (P less than 0.01) and IL1B (P less thann 0.05) gene expression levels were found to be statistically significant, while IL6 and TNF gene expressions were not significant. While the IL6 and TNF gene expression differences are insignificant between the groups, numerically higher level of gene expression was observed in the CON group. Overall results of the study suggested that the rubber mat floor type has a positive impact on both the animal welfare and the udder health.

Abstract 12423: Normoxic Therapy Attenuated Oxidative Stress Related mRNA Gene Expressions in a Post-Cardiac Arrest Rat Model

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Tomoaki Aoki ◽  
Koichiro Shinozaki ◽  
Yu Okuma ◽  
Kei Hayashida ◽  
Ryosuke Takegawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cardiac Arrest ◽  
Signaling Pathways ◽  
Expression Patterns ◽  
Expression Levels ◽  
Mrna Gene ◽  
The Brain ◽  
Mrna Gene Expression ◽  
Gene Expression Levels

Objective: We recently reported that post-resuscitation normoxic therapy attenuates oxidative stress in multiple organs and improves post-cardiac arrest (CA) organ injury, oxygen metabolism, and survival. Yet, detailed mechanisms of gene expression patterns and signaling pathways mitigated by normoxic therapy have not been elucidated. Therefore, we assessed post-resuscitation normoxic therapy-modified gene expression of oxidative stress-related signaling molecules. Methods: Rats were resuscitated from 10 minutes of asphyxial CA and divided into 2 groups: those that inhaled 100% supplemental O 2 (CA-FIO2 1.0) and those that inhaled 30% supplemental O 2 (CA-FIO2 0.3). Control groups were also prepared for comparison (control-FIO2 1.0, control-FIO2 0.3). At 2 hours after resuscitation, brain and heart tissues were collected, and mRNA purifications followed by real-time PCR measurements were performed to compare gene expression of hyperoxia-induced inflammatory and apoptosis-related signaling pathways amongst these groups. Results: In the brain, relative IL-1 beta mRNA gene expression levels, which represent inflammatory signaling pathways, increased post-CA (8.1±2.3 in CA-FIO2 1.0 and 1.0±0.4 in control-FIO2 0.3, p<0.05), but were significantly attenuated by normoxic therapy (2.3±0.2 in CA-FIO2 0.3, p<0.05). Likewise, normoxic therapy significantly reduced oxidative stress-induced inflammatory (NFKB1, TGFB1, MAPK14, TRAF6) and apoptosis-related (BAX, EGF) mRNA gene expression levels in the brain, whereas no statistical differences were detected in the heart. Conclusions: Post-CA normoxic therapy significantly attenuated the gene expression of oxidative stress-induced inflammation and apoptosis in the brain, while there were no remarkable changes in the heart. Therefore, it is inferred that the heart is more tolerant to hyperoxic injury compared to the brain.

scholarly journals Hard wiring of normal tissue-specific chromosome-wide gene expression levels is an additional factor driving cancer type-specific aneuploidies

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sushant Patkar ◽  
Kerstin Heselmeyer-Haddad ◽  
Noam Auslander ◽  
Daniela Hirsch ◽  
Jordi Camps ◽  
...  
Keyword(s):  
Gene Expression ◽  
Normal Tissue ◽  
Cancer Type ◽  
Tissue Specific ◽  
Expression Levels ◽  
Specific Distribution ◽  
Tumor Origin ◽  
Chromosome Arm ◽  
Gains And Losses ◽  
Gene Expression Levels

Abstract Background Many carcinomas have recurrent chromosomal aneuploidies specific to the tissue of tumor origin. The reason for this specificity is not completely understood. Methods In this study, we looked at the frequency of chromosomal arm gains and losses in different cancer types from the The Cancer Genome Atlas (TCGA) and compared them to the mean gene expression of each chromosome arm in corresponding normal tissues of origin from the Genotype-Tissue Expression (GTEx) database, in addition to the distribution of tissue-specific oncogenes and tumor suppressors on different chromosome arms. Results This analysis revealed a complex picture of factors driving tumor karyotype evolution in which some recurrent chromosomal copy number reflect the chromosome arm-wide gene expression levels of the their normal tissue of tumor origin. Conclusions We conclude that the cancer type-specific distribution of chromosomal arm gains and losses is potentially “hardwiring” gene expression levels characteristic of the normal tissue of tumor origin, in addition to broadly modulating the expression of tissue-specific tumor driver genes.

scholarly journals Genetic Variants Associated mRNA Stability in Lung

2021 ◽  
Author(s):  
Jian-Rong Li ◽  
Mabel Tang ◽  
Yafang Li ◽  
Christopher I Amos ◽  
Chao Cheng
Keyword(s):  
Gene Expression ◽  
Mrna Stability ◽  
Genetic Variants ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Tissue Expression ◽  
Rna Seq ◽  
Genetic Traits ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Background: Expression quantitative trait loci (eQTLs) analyses have been widely used to identify genetic variants associated with gene expression levels to understand what molecular mechanisms underlie genetic traits. The resultant eQTLs might affect the expression of associated genes through transcriptional or post-transcriptional regulation. In this study, we attempt to distinguish these two types of regulation by identifying genetic variants associated with mRNA stability of genes (stQTLs).Results: Here, we presented a computational framework that take the advantage of recently developed methods to infer the mRNA stability of genes based on RNA-seq data and performed association analysis to identify stQTLs. Using the Genotype-Tissue Expression (GTEx) lung RNA-Seq data, we identified a total of 142,801 stQTLs for 3,942 genes and 186,132 eQTLs for 4,751 genes from 15,122,700 genetic variants for 13,476 genes, respectively. Interesting, our results indicated that stQTLs were enriched in the CDS and 3’UTR regions, while eQTLs are enriched in the CDS, 3’UTR, 5’UTR, and upstream regions. We also found that stQTLs are more likely than eQTLs to overlap with RNA binding protein (RBP) and microRNA (miRNA) binding sites. Our analyses demonstrate that simultaneous identification of stQTLs and eQTLs can provide more mechanistic insight on the association between genetic variants and gene expression levels.

scholarly journals Gene expression levels of DNA methyltransferase enzymes in Shank3-deficient mouse model of autism during early development

2021 ◽  
Vol 55 (4) ◽  
pp. 234-237
Author(s):  
Annamaria Srancikova ◽  
Alexandra Reichova ◽  
Zuzana Bacova ◽  
Jan Bakos
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Brain Development ◽  
Early Development ◽  
Molecular Mechanisms ◽  
Altered Expression ◽  
Expression Levels ◽  
The Brain ◽  
Deficient Mice ◽  
Gene Expression Levels

Abstract Objectives. The balance between DNA methylation and demethylation is crucial for the brain development. Therefore, alterations in the expression of enzymes controlling DNA methylation patterns may contribute to the etiology of neurodevelopmental disorders, including autism. SH3 and multiple ankyrin repeat domains 3 (Shank3)-deficient mice are commonly used as a well-characterized transgenic model to investigate the molecular mechanisms of autistic symptoms. DNA methyltransferases (DNMTs), which modulate several cellular processes in neurodevelopment, are implicated in the pathophysiology of autism. In this study, we aimed to describe the gene expression changes of major Dnmts in the brain of Shank3-deficient mice during early development. Methods and Results. The Dnmts gene expression was analyzed by qPCR in 5-day-old homo-zygous Shank3-deficient mice. We found significantly lower Dnmt1 and Dnmt3b gene expression levels in the frontal cortex. However, no such changes were observed in the hippocampus. However, significant increase was observed in the expression of Dnmt3a and Dnmt3b genes in the hypothalamus of Shank3-deficient mice. Conclusions. The present data indicate that abnormalities in the Shank3 gene are accompanied by an altered expression of DNA methylation enzymes in the early brain development stages, therefore, specific epigenetic control mechanisms in autism-relevant models should be more extensively investigated.

Expression Level Of A Coagulation Factor Gene, F13A1 Defines Characteristic Subpopulations Of Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4888-4888
Author(s):  
Csongor Kiss ◽  
Katalin Gyurina ◽  
Gábor Kiss ◽  
Silvia Bresolin ◽  
Zsuzsa Hevessy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Tyrosine Kinases ◽  
Lymphoblastic Leukemia ◽  
Coagulation Factor ◽  
Expression Level ◽  
Expression Levels ◽  
Gene Expression Levels

Abstract Using multiparameter flow cytometry, Western blot, ELISA and laser scanning microscopy, leukemic B-cell progenitor lymphoblasts were identified as a novel expression site of coagulation factor XIII subunit A (FXIIIA) (Kiss et al Thromb Haemost 2006). Three-year overall survival (OS) of children with FXIIIA-positive acute lymphoblastic leukemia (ALL) was significantly higher (87%) than 3-yr OS of patients with FXIIIA-negative ALL (65%). Here we report on gene expression profiles (GEP) associated with FXIIIA-positive vs. FXIIIA–negative childhood (ch)ALL. Finnally, the expression levels of F13A1 gene in cytogenetic subgroups were investigated. GEP of 11 FXIIIA-positive and 9 FXIIIA-negative samples of patients treated at the Department of Hematology-Oncology, University of Debrecen was investigated using HG-U 133 plus 2.0 Affymetrix Platform Array. Expression sequence tags (EST) characterized by expression levels with at least 2 logs difference among FXIIIA-positive vs. FXIIIA-negative samples were selected and validated with real-time quantitative PCR. Extending the analysis, we have searched the database containing GEPs of 317 children with ALL treated at the Division of Hemato-Oncology, Department of Women’s and Children’s Health, University of Padova, using R package and Partek Genomic Suite softwares. FXIIIA-positive and FXIIIA-negative samples exhibited a characteristically different GEP. In the FXIIIA-positive samples one of the overexpressed genes was F13A1. FXIIIA-negative samples contained two characteristic groups of overexpressed genes. One of these consisted of genes participating in B-cell development: EBF1, IKZF1 and PAX5. The second set consisted of genes encoding for tyrosine kinases: JAK1, JAK3, NC07523, NC08002, NC06523, NC08345 and for serine-threonine kinase NC00027. In contrast, FXIIIA-positive samples contained only two overexpressed tyrosine kinases: C-KIT and JAK2. A wide variation of F13A1 expression levels of the 317 Padova patients was observed. Since expression level of FXIIIA protein of these patients has not been determined, we have arbitrarily defined F13A1 gene expression levels below 106 as “low” and gene expression levels exceeding 109 as “high”. Considering these two groups, we have investigated the distribution of F13A1 expression among the known cytogenetic subgroups of ALL. Low F13A1 expression was prevalent among “B-other” samples, high F13A1 expression was associated with t(1;19). The pattern of overexpressed ESTs, accumulation of low F13A1 expressing samples in the “B-other” cytogenetic group of ALL and the unfavorable disease outcome of FXIIIA-negative cases may suggest a possible overlap between FXIIIA-negative ALL and BCR-ABL1-like ALL identified recently in the “B-other” group. The nature and extent of this overlap will be investigated prospectively in the BFM ALL-IC 2009 clinical trial. In contrast, high expression levels of F13A1 accumulated preferentially within the t(1;19) genetic group, associated with a good prognosis. Detection of FXIIIA expression by flow cytometry may offer an easy and non-expensive tool for defining new prognostic subpopulations of ALL. Grant support TÁMOP 4.2.2.A-11/1/KONV-2012-0025 project (CK, KG, HZ, IG, IS and JK). The project is co-financed by the European Union and the European Social Fund and the AIRC (Associazione Italiana Ricerca su Cancro; SB) project. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Integrative genomic strategies applied to a lymphoblast cell line model reveal specific transcriptomic signatures associated with clozapine response

2020 ◽  
Author(s):  
SAJ de With ◽  
APS Ori ◽  
T Wang ◽  
SL Pulit ◽  
E Strengman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Adverse Effects ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Disease Risk ◽  
Density Lipoprotein ◽  
Expression Levels ◽  
Genome Wide ◽  
Gene Expression Levels

AbstractClozapine is an important antipsychotic drug. However, its use is often accompanied by metabolic adverse effects and, in rare instances, agranulocytosis. The molecular mechanisms underlying these adverse events are unclear. To gain more insights into the response to clozapine at the molecular level, we exposed lymphoblastoid cell lines (LCLs) to increasing concentrations of clozapine and measured genome-wide gene expression and DNA methylation profiles. We observed robust and significant changes in gene expression levels due to clozapine (n = 463 genes at FDR < 0.05) affecting cholesterol and cell cycle pathways. At the level of DNA methylation, we find significant changes upstream of the LDL receptor, in addition to global enrichments of regulatory, immune and developmental pathways. By integrating these data with human tissue gene expression levels obtained from the Genotype-Tissue Expression project (GTEx), we identified specific tissues, including liver and several tissues involved in immune, endocrine and metabolic functions, that clozapine treatment may disproportionately affect. Notably, differentially expressed genes were not enriched for genome-wide disease risk of schizophrenia or for known psychotropic drug targets. However, we did observe a nominally significant association of genetic signals related to total cholesterol and low-density lipoprotein levels. Together, these results shed light on the biological mechanisms through which clozapine functions. The observed associations with cholesterol pathways, its genetic architecture and specific tissue effects may be indicative of the metabolic adverse effects observed in clozapine users. LCLs may thus serve as a useful tool to study these molecular mechanisms further.

scholarly journals Novel Insights into the Prognosis and Immunological Value of the SLC35A (Solute Carrier 35A) Family Genes in Human Breast Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1804
Author(s):  
Hoang Dang Khoa Ta ◽  
Do Thi Minh Xuan ◽  
Wan-Chun Tang ◽  
Gangga Anuraga ◽  
Yi-Chun Ni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Predictive Values ◽  
Expression Levels ◽  
Solute Carrier ◽  
Gene Expression Levels

According to statistics 2020, female breast cancer (BRCA) became the most commonly diagnosed malignancy worldwide. Prognosis of BRCA patients is still poor, especially in population with advanced or metastatic. Particular functions of each members of the solute carrier 35A (SLC35A) gene family in human BRCA are still unknown regardless of awareness that they play critical roles in tumorigenesis and progression. Using integrated bioinformatics analyses to identify therapeutic targets for specific cancers based on transcriptomics, proteomics, and high-throughput sequencing, we obtained new information and a better understanding of potential underlying molecular mechanisms. Leveraging BRCA dataset that belongs to The Cancer Genome Atlas (TCGA), which were employed to clarify SLC35A gene expression levels. Then we used a bioinformatics approach to investigate biological processes connected to SLC35A family genes in BRCA development. Beside that, the Kaplan–Meier estimator was leveraged to explore predictive values of SLC35A family genes in BCRA patients. Among individuals of this family gene, expression levels of SLC35A2 were substantially related to poor prognostic values, result from a hazard ratio of 1.3 (with 95 percent confidence interval (95% CI: 1.18–1.44), the p for trend (ptrend) is 3.1 × 10−7). Furthermore, a functional enrichment analysis showed that SLC35A2 was correlated with hypoxia-inducible factor 1A (HIF1A), heat shock protein (HSP), E2 transcription factor (E2F), DNA damage, and cell cycle-related signaling. Infiltration levels observed in specific types of immune cell, especially the cluster of differentiation found on macrophages and neutrophils, were positively linked with SLC35A2 expression in multiple BRCA subclasses (luminal A, luminal B, basal, and human epidermal growth factor receptor 2). Collectively, SLC35A2 expression was associated with a lower recurrence-free survival rate, suggesting that it could be used as a biomarker in treating BRCA.

scholarly journals Cancer-type specific aneuploidies hard-wire chromosome-wide gene expression patterns of their tissue of origin

2019 ◽  
Author(s):  
Noam Auslander ◽  
Kerstin Heselmeyer-Haddad ◽  
Sushant Patkar ◽  
Daniela Hirsch ◽  
Jordi Camps ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Tumor Evolution ◽  
Cancer Type ◽  
Expression Levels ◽  
Normal Tissues ◽  
Chromosome Arm ◽  
Tissue Of Origin ◽  
Chromosomal Aneuploidies ◽  
Gene Expression Levels

SUMMARYMost carcinomas have characteristic chromosomal aneuploidies specific to the tissue of tumor origin. The reason for this specificity is unknown. As aneuploidies directly affect gene expression, we hypothesized that cancer-type specific aneuploidies, which emerge at early stages of tumor evolution, confer adaptive advantages to the physiological requirements of the tissue of origin. To test this hypothesis, we compared chromosomal aneuploidies reported in the TCGA database to chromosome arm-wide gene expression levels of normal tissues from the GTEx database. We find that cancer-type specific chromosomal aneuploidies mirror differential gene expression levels specific to the respective normal tissues which cannot be explained by copy number alterations of resident cancer driver genes. We propose that cancer-type specific aneuploidies “hard-wire” chromosome arm-wide gene expression levels present in normal tissues, favoring clonal expansion and tumorigenesis.One sentence summaryThe clonal evolution of cancer is initiated by tissue-specific transcriptional requirements

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