Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA116865 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Glomus tumors (GT) are perivascular tumors mostly occurring in the distal extremities. Rare cases occur in the digestive tract and may be misdiagnosed with neuroendocrine or gastrointestinal stromal tumors. We aimed to specify the features of GT of the upper digestive tract. We investigated two cases using whole exome sequencing (WES) and RNA-sequencing, and present clinical, histological, phenotypic and molecular features of 16 cases. WES did not reveal any commonly involved cellular pathway. By contrast, RNA-sequencing disclosed a t(1:5)(p13;q32) translocation between MIR143HG and NOTCH2 in both cases. The deducted fusion protein sequence corresponded to the NOTCH2 intracellular domain known as NICD2, which acts as transcription factor. These data were confirmed by high expression of the transcripts of genes targeted by NOTCH cellular pathway (HES and HEY gene families). In our retrospective multicentric series of 16 GT of upper digestive tract MIR143HG-NOTCH2 translocation was detected in 14 (88%) cases. By contrast, it was present in only 2/6 (33%) GT of the distal extremities. Most digestive GT raised from the stomach (n=13), and the others from duodenal (2) or oesophagous (1). All digestive GT were positive for α-smooth muscle actin and transgelin, and negative for cytokeratin AE1/AE3, chromogranine, DOG1, KIT and S100. Most cases were positive for H-caldesmon (n=14) and/or for synaptophysin (n=10). Desmin, CD34 or CD56 were positive in only one case each. Nuclear expression of NOTCH2 was detected in the 14 cases containing the fusion transcripts. The present study shows that MIR143HG-NOTCH2 translocation is present in most digestive GT. This fusion transcript is associated with activation of the NOTCH2 pathway and may drive tumor development. Detection of nuclear NOTCH2 expression may be helpful for diagnosis.
2019-08-31 | GSE118896 | GEO
Project description:Klotho functions as an aging suppressor, which, in mice, extends lifespan when overexpressed and accelerates development of aging-like phenotypes when disrupted. Klotho is mainly expressed in brain and kidney and is secreted into the serum and CSF. We have previously shown that Klotho is reduced in brains of old monkeys, rats and mice. We further reported the ability of Klotho to enhance oligodendrocyte differentiation and myelination. Here we examined the effects of Klotho on MO3.13, a human oligodendroglioma cell line in order to determine the potential role of Klotho as a tumor suppressor. We show that exogenous Klotho affects the ERK and Akt signaling pathways and decreases the proliferative abilities of MO3.13 cells. Furthermore, microarray analysis of Klotho-treated MO3.13 cells reveals a massive change in gene expression with 80% of the differentially expressed genes being downregulated. Using gene set enrichment analysis we predicted potential transcription factors involved in regulating Klotho-treated MO3.13 cells and found that these cells are highly enriched in the gene sets, that are similarly observed in cancer, cardiovascular disease, stress, aging and hormone-related chemical and genetic perturbations. Since Klotho is downregulated in all brain tumors tested to date, enhancing Klotho has therapeutic potential for treating brain malignancies. 6 Samples
2014-06-09 | E-GEOD-51536 | biostudies-arrayexpress
Project description:Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice exhibited similar gene expression profiling to corresponding primary tumors. Gene expression profiling of tumors and tumorgrafts displayed different signatures for BAP1- and PBRM1-deficient samples. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities. The RNA of clear-cell renal cell carcinoma (ccRCC) primary tumors, tumors growing in immunodeficient mice (tumorgrafts), and normal kidney cortices were labeled and hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays.
2012-06-09 | E-GEOD-36895 | biostudies-arrayexpress
Project description:Identification of ZDHHC14 as a novel tumor suppressor gene commonly downregulated in human cancers
| PRJNA150645 | ENA
Project description:Using H3K27ac HiChIP assays to link genetic variants to target genes in upper digestive cancers
2024-02-25 | GSE235431 | GEO
Project description:Using H3K27ac ChIP-seq assays followed by sequencing to identify regulatory elements in upper digestive cancers
2024-02-25 | GSE240213 | GEO
Project description:We investigated the involvement of microRNAs (miRNAs) in gastric cancers. MiRNA expression was profiled from 40 cancerous and 40 non-cancerous tissues obtained from the National Cancer Centre, Singapore, and Singhealth Tissue Repository, Singapore. We identified 80 differentially expressed miRNAs in tumors compared with normal tissues. Among these miRNAs, we identified hsa-mir-486-5p (mir-486) as a significantly downregulated miRNA in GC. Subsequent functional characterization revealed that mir-486 playing a tumor suppressor role. We also observed frequent genomic deletion of mir-486 in 20-30% of GCs. To our knowledge, mir-486 represents one of the first tumor suppressor miRNAs in GC inactivated through genomic deletion. MiRNA expression was profiled on Agilent Human miRNA Microarrays (V2) representing 723 human and 76 human viral miRNAs in 40 normal and 40 cancerous gastric tissues.
2011-08-01 | E-GEOD-23739 | biostudies-arrayexpress
Project description:The present microarray studies the differential transcription levels of various genes upon overexpression of tumor suppressor protein SMAR1. The results will lead us to potential targets which are either up/downregulated by SMAR1. Experiment Overall Design: Agilent two-color experiment,Organism: Human ,Slides, Agilent’s Human Microarray G4110B with 22000 features, Labeling kit: Agilents Low input RNA linear amplification Kit Cat # 5184-3523, Labeling Method: T7 promoter based-linear amplification to generate labeled complementary RNA
2009-09-05 | E-GEOD-17795 | biostudies-arrayexpress
Project description:Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice retained >92% of mutations and exhibited similar DNA copy number alterations to corresponding primary tumors. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities. The genomic DNA of clear-cell renal cell carcinoma (ccRCC) primary tumors, tumors growing in immunodeficient mice (tumorgrafts), and normal samples were labeled and hybridized to Affymetrix SNP arrays 6.0.
2012-06-09 | E-GEOD-25540 | biostudies-arrayexpress
Project description:This experiment was an aCGH study on 86 prostate tumors samples. The samples were profiled on Agilent Human Genome 44karrays to identify recurrent regions of deletion and amplification, thus revealing potential new tumor suppressor genes and/or oncogenes involved in prostate cancer. The CGH profile on the 44k arrays revealed a deletion at 5q21 in 17% of samples. CGH analysis of 86 prostate tumor samples.
2011-12-19 | E-GEOD-29227 | biostudies-arrayexpress