Ena-DATASET-BGI-31-12-2014-03:23:33:590-567 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001001118 | EGA |
REPOSITORIES: EGA
Publications
Mutational landscape of gastric adenocarcinoma in Chinese: implications for prognosis and therapy.
Chen Kexin K Yang Da D Li Xiangchun X Sun Baocun B Song Fengju F Cao Wenfeng W Brat Daniel J DJ Gao Zhibo Z Li Haixin H Liang Han H Zhao Yanrui Y Zheng Hong H Li Miao M Buckner Jan J Patterson Scott D SD Ye Xiang X Reinhard Christoph C Bhathena Anahita A Joshi Deepa D Mischel Paul S PS Croce Carlo M CM Wang Yi Michael YM Raghavakaimal Sreekumar S Li Hui H Lu Xin X Pan Yang Y Chang Han H Ba Sujuan S Luo Longhai L Cavenee Webster K WK Zhang Wei W Hao Xishan X
Proceedings of the National Academy of Sciences of the United States of America 20150112 4
Gastric cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with three primary tumors and two matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC). The HiC subt ...[more]
Similar Datasets
Project description:Gastric Cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with 3 primary tumours and 2 matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC).
| EGAS00001001056 | EGA
Project description:Mathematical modeling of immune modulation by glucocorticoids
Konstantin Yakimchuk
https://doi.org/10.1016/j.biosystems.2019.104066
Abstract
The cellular and molecular mechanisms of immunomodulatory actions of glucocorticoids (GC) remain to be identified. Using our experimental findings, a mathematical model based on a system of ordinary differential equations for characterization of the regulation of anti-tumor immune activity by the both direct and indirect GC effects was generated to study the effects of GC treatment on effector CD8+ T cells, GC-generated tolerogenic dendritic cells (DC), regulatory T cells and the growth of lymphoma cells. In addition, we compared the data from in vivo and in silico experiments. The mathematical simulations indicated that treatment with GCs may suppress anti-tumor immune response in a dose-dependent manner. The model simulations were in line with earlier experimental observations of inhibitory effects of GCs on T and NK cells and DCs. The results of this study might be useful for predicting clinical outcomes in patients receiving GC therapy.
2020-01-06 | MODEL1912170005 | BioModels
Project description:Ig diversification occurs in peripheral lymphoid organs after establishment of central tolerance during B cell development. In germinal centers (GCs), somatic hypermutation of Ig genes occurs in dark zones, followed by selection of mutated clones in light zones (LZs). This generates high-affinity Ig receptors to pathogens but can also produce autoreactive Ig receptors, which are removed by selection mechanisms that are incompletely understood. The ubiquitin ligase Itch prevents the emergence of autoimmune disease and autoantibodies in humans and mice, and patients lacking Itch develop potentially fatal autoimmune diseases; yet, how Itch regulates GC B cells is not well understood. By studying Itch-deficient mice, we have recently shown that Itch directly limits the magnitude of GC responses. Proteomic profiling of GC B cells uncovered that Itch-deficient cells exhibit high mTORC1 and Myc activity, hallmarks of positive selection. Bone marrow chimera and adoptive transfer experiments revealed that B cell Itch restricts noncycling LZ cells. These results support, t our knowledge, a novel role for Itch in skewing selection of GC B cells to restrict LZ accumulation and shape GC-derived humoral immunity. Determining how B cells integrate cues within GCs to navigate through LZs and dark zones will aid in understanding how autoreactive clones emerge from GCs in people with autoimmune disease.
2024-11-12 | PXD040978 | Pride
Project description:<p>This project aims to conduct genome-wide association studies (GWAS) in two anatomically different upper gastrointestinal (UGI) cancer sites in two populations with distinctly different disease rates and genetic profiles. One population has very high rates for both esophageal squamous cell carcinomas (ESCCs) and gastric cancers (GCs) and is comprised of Asians (<b>the "Asian UGI GWAS"</b>), while the other population has low rates of ESCC and GC and includes non-Asians from the Americas, Europe, and Australia (<b>the "Non-Asian UGI GWAS"</b>).</p> <p>Study participants for the Asian UGI GWAS reported here (Illumina 660W Quad chip) were drawn from 2 studies, the Shanxi Upper Gastrointestinal Cancer Genetics Project (Shanxi) and the Linxian Nutrition Intervention Trial (NIT), a prospective cohort, and included a total of 1898 ESCCs, 1625 GCs, and 2100 controls. For the 2nd phase (8 TaqMan SNPs), additional subjects from Shanxi and NIT as well as subjects from the Shanghai Men's Health Study (SMHS), the Shanghai Women's Health Study (SWHS), and the Singapore Chinese Health Study (SCHS) were also included (217 ESCCs, 615 GCs, 1202 controls). Altogether 2115 ESCCs, 2240 GCs, and 3302 controls were genotyped in this study.</p>
| phs000361 | dbGaP
Project description:A large-scale characterization of the methylation states of candidate CpG islands (CGIs) throughout the gastric cancer methylome has not previously been conducted. Genome-wide DNA methylation profiles were compared between 4 metastatic and 4 non-metastatic gastric carcinomas (GCs) and their surgical margins (SMs). The GC genome showed significantly higher proportions of hypomethylation in the promoter and exon-1 regions, as well as increased hypermethylation of intragenic fragments when compared to SMs. Differential methylation was observed in CGIs near transcription start sites of 546 genes between GCs and SMs, and 601 genes between metastatic and non-metastatic GCs. From the list of differentially methylated CGIs, 68 candidate genes and 10 known tumor-related genes were selected for further characterization based on their known molecular function using DHPLC. Significant differential methylation was validated in the CGIs of 15 genes between GCs and SMs (Ps<0.05) and confirmed using bisulfite-sequencing. These genes include BMP3, BNIP3, CDKN2A, ECEL1, ELK1, GFRA1, HOXD10, KCNH1, PSMD10, PTPRT, SIGIRR, SRF, TBX5, TFPI2, and ZNF382. Hypomethylation of CGIs correlated with up-regulation of GFRA1 expression in GCs, while hypermethylation of other genes inactivated their transcription. Most importantly, prevalence of GFRA1, SRF, and ZNF382 methylation alterations were inversely and coordinately associated with GC metastasis and the patients’ overall survival throughout discovery and testing cohorts in China as well as independent validation cohorts in Japan and Korea. In conclusion, methylation changes in the CGIs of 15 genes correlated strongly with GC development. GFRA1 hypomethylation and SRF and ZNF382 hypermethylation are potential synergistic biomarkers for the prediction of GC metastasis. To identify differential methylation of CGIs related to GC development and metastasis, genome-wide DNA methylation changes in 8 pairs of GC and SM samples were analysed using the MCAM assay with a 99K custom-designed Agilent oligonucleotide microarray composed of 99,027 probes targeting 6,177 unique protein-coding genes containing at least two methylation-sensitive/insensitive SmaI/ XmaI restriction sites (CCC|GGG/ C|CmCGGG) as described in Shen et al, PLoS Genet 3, 2023-2036 (2007).
2014-06-02 | E-GEOD-47724 | biostudies-arrayexpress
Project description:Follicular helper T (Tfh) cells access the B cell follicle to promote antibody responses, and are particularly important for germinal center (GC) reactions. However, the molecular mechanisms of how Tfh cells are physically associated with GCs are incompletely understood. Here we report that the sphingosine-1-phosphate receptor 2 (S1PR2) gene is highly expressed in a subpopulation of Tfh cells that localizes in GCs. S1PR2-deficient Tfh cells exhibited reduced accumulation in GCs due to their impaired retention. T cells deficient in both S1PR2 and CXCR5 were ineffective in supporting GC responses compared to T cells deficient only in CXCR5. These results suggest that S1PR2 and CXCR5 cooperatively regulate localization of Tfh cells in GCs to support GC responses. Venus-high Tfh, Venus-low Tfh, PD1-intermediate Th, PD1-low Th and naïve CD4+ T cells were sorted on FACSAria from immunized S1pr2V/+ mice or control mice for RNA extraction and hybridization on Affimetrix microarrays.
2014-05-30 | E-GEOD-56883 | biostudies-arrayexpress
Project description:Glucocorticoids (GCs) are a mainstay of contemporary, multi-drug chemotherapy in the treatment of acute lymphoblastic leukemia (ALL). Although overall survival rates of childhood ALL have improved, resistance to antileukemic agents remains a major clinical concern. In particular, resistance to GCs is predictive of ALL relapse and poor clinical outcome, and it therefore represents a major hurdle limiting further improvements in survival rates. While advances have been made in identifying genes and transcriptional signatures implicated in ALL GC resistance, there remains an insufficient understanding of the impact of glucocorticoid response element (GRE) alterations in GC resistance. To therefore better understand the role of gene regulatory alterations in GC resistance, we comprehensively mapped the GC gene regulatory network in two ALL cell lines using orthogonal functional genomic assays and identified tens of thousands of GREs in the ALL genome. A closer examination revealed binding profiles that were consistent with the long-range flexible billboard model of gene regulation. GCs also induced the formation of over 250 super-enhancers, and these GC-responsive super-enhancers control the expression of genes mediating GC resistance. By further integrating our results with genetic and epigenetic data in primary ALL cells from patient cohorts at St. Jude, we identified 45 DNA sequence variants associated with ex vivo GC resistance that map to GREs and validated an associated variant within the TLE1 gene locus. We also uncovered that 1929 accessible chromatin sites associated with ex vivo GC resistance were significantly enriched at GREs. A CRISPR interference screen of these elements validated their effects on GC resistance. Overall, these data suggest that GCs initiate pervasive, genome-wide effects on the leukemia epigenome and transcriptome, while genetic and epigenetic alterations to GREs are mechanisms contributing to GC resistance in childhood ALL.
2022-08-25 | GSE190884 | GEO
Project description:Glucocorticoids (GCs) are a mainstay of contemporary, multi-drug chemotherapy in the treatment of acute lymphoblastic leukemia (ALL). Although overall survival rates of childhood ALL have improved, resistance to antileukemic agents remains a major clinical concern. In particular, resistance to GCs is predictive of ALL relapse and poor clinical outcome, and it therefore represents a major hurdle limiting further improvements in survival rates. While advances have been made in identifying genes and transcriptional signatures implicated in ALL GC resistance, there remains an insufficient understanding of the impact of glucocorticoid response element (GRE) alterations in GC resistance. To therefore better understand the role of gene regulatory alterations in GC resistance, we comprehensively mapped the GC gene regulatory network in two ALL cell lines using orthogonal functional genomic assays and identified tens of thousands of GREs in the ALL genome. A closer examination revealed binding profiles that were consistent with the long-range flexible billboard model of gene regulation. GCs also induced the formation of over 250 super-enhancers, and these GC-responsive super-enhancers control the expression of genes mediating GC resistance. By further integrating our results with genetic and epigenetic data in primary ALL cells from patient cohorts at St. Jude, we identified 45 DNA sequence variants associated with ex vivo GC resistance that map to GREs and validated an associated variant within the TLE1 gene locus. We also uncovered that 1929 accessible chromatin sites associated with ex vivo GC resistance were significantly enriched at GREs. A CRISPR interference screen of these elements validated their effects on GC resistance. Overall, these data suggest that GCs initiate pervasive, genome-wide effects on the leukemia epigenome and transcriptome, while genetic and epigenetic alterations to GREs are mechanisms contributing to GC resistance in childhood ALL.
2022-08-25 | GSE176278 | GEO
Project description:Glucocorticoids (GCs) are a mainstay of contemporary, multi-drug chemotherapy in the treatment of acute lymphoblastic leukemia (ALL). Although overall survival rates of childhood ALL have improved, resistance to antileukemic agents remains a major clinical concern. In particular, resistance to GCs is predictive of ALL relapse and poor clinical outcome, and it therefore represents a major hurdle limiting further improvements in survival rates. While advances have been made in identifying genes and transcriptional signatures implicated in ALL GC resistance, there remains an insufficient understanding of the impact of glucocorticoid response element (GRE) alterations in GC resistance. To therefore better understand the role of gene regulatory alterations in GC resistance, we comprehensively mapped the GC gene regulatory network in two ALL cell lines using orthogonal functional genomic assays and identified tens of thousands of GREs in the ALL genome. A closer examination revealed binding profiles that were consistent with the long-range flexible billboard model of gene regulation. GCs also induced the formation of over 250 super-enhancers, and these GC-responsive super-enhancers control the expression of genes mediating GC resistance. By further integrating our results with genetic and epigenetic data in primary ALL cells from patient cohorts at St. Jude, we identified 45 DNA sequence variants associated with ex vivo GC resistance that map to GREs and validated an associated variant within the TLE1 gene locus. We also uncovered that 1929 accessible chromatin sites associated with ex vivo GC resistance were significantly enriched at GREs. A CRISPR interference screen of these elements validated their effects on GC resistance. Overall, these data suggest that GCs initiate pervasive, genome-wide effects on the leukemia epigenome and transcriptome, while genetic and epigenetic alterations to GREs are mechanisms contributing to GC resistance in childhood ALL.
2022-08-25 | GSE175483 | GEO
Project description:Glucocorticoids (GCs) are a mainstay of contemporary, multi-drug chemotherapy in the treatment of acute lymphoblastic leukemia (ALL). Although overall survival rates of childhood ALL have improved, resistance to antileukemic agents remains a major clinical concern. In particular, resistance to GCs is predictive of ALL relapse and poor clinical outcome, and it therefore represents a major hurdle limiting further improvements in survival rates. While advances have been made in identifying genes and transcriptional signatures implicated in ALL GC resistance, there remains an insufficient understanding of the impact of glucocorticoid response element (GRE) alterations in GC resistance. To therefore better understand the role of gene regulatory alterations in GC resistance, we comprehensively mapped the GC gene regulatory network in two ALL cell lines using orthogonal functional genomic assays and identified tens of thousands of GREs in the ALL genome. A closer examination revealed binding profiles that were consistent with the long-range flexible billboard model of gene regulation. GCs also induced the formation of over 250 super-enhancers, and these GC-responsive super-enhancers control the expression of genes mediating GC resistance. By further integrating our results with genetic and epigenetic data in primary ALL cells from patient cohorts at St. Jude, we identified 45 DNA sequence variants associated with ex vivo GC resistance that map to GREs and validated an associated variant within the TLE1 gene locus. We also uncovered that 1929 accessible chromatin sites associated with ex vivo GC resistance were significantly enriched at GREs. A CRISPR interference screen of these elements validated their effects on GC resistance. Overall, these data suggest that GCs initiate pervasive, genome-wide effects on the leukemia epigenome and transcriptome, while genetic and epigenetic alterations to GREs are mechanisms contributing to GC resistance in childhood ALL.
2022-08-25 | GSE188713 | GEO