Filters
Technology
Platform
GSE19987
Homo sapiens
125 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Pheochromocytomas, catecholamine-secreting tumors of neural crest origin, are frequently hereditary. However, the molecular basis of the majority of these tumors is unknown. We identified the transmembrane-encoding gene TMEM127 on chromosome 2q11 as a new pheochromocytoma susceptibility gene. In a cohort of 103 samples, we detected truncating germline TMEM127 mutations in approximately 30% of familial tumors and about 3% of sporadic-appearing pheochromocytomas without a known genetic cause. The wild-type allele was consistently deleted in tumor DNA, suggesting a classic mechanism of tumor suppressor gene inactivation. Pheochromocytomas with mutations in TMEM127 are transcriptionally related to tumors bearing NF1 mutations and, similarly, show hyperphosphorylation of mammalian target of rapamycin (mTOR) effector proteins. Accordingly, in vitro gain-of-function and loss-of-function analyses indicate that TMEM127 is a negative regulator of mTOR. TMEM127 dynamically associates with the endomembrane system and colocalizes with perinuclear (activated) mTOR, suggesting a subcompartmental-specific effect. Our studies identify TMEM127 as a tumor suppressor gene and validate the power of hereditary tumors to elucidate cancer pathogenesis.
Publication Title
Germline mutations in TMEM127 confer susceptibility to pheochromocytoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
Description
Pheochromocytomas/paragangliomas are the most heritable of all tumors. However, there are still cases that are not explained by mutations in the known genes. We aimed to identify the genetic cause of disease in a patient strongly suspected of having hereditary tumors. We identified a novel de novo mutation in DNMT3A, affecting a highly conserved residue. Among other results from other techniques, a different global expression profile was observed in the patient carrying the mutated DNMT3A compared to controls (parents) by RNA-seq
Publication Title
Gain-of-function mutations in DNMT3A in patients with paraganglioma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 436 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Heart failure (HF) is the most common cause of morbidity and mortality in the developed countries, especially considering the present demographic tendencies in those populations.
Publication Title
Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 97 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Despite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI) is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients.
Publication Title
Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Cell migration is central to many biological processes including embryonic development, wound healing, and cancer progression. Cell migration is sensitive to environmental stiffness, and many cell types exhibit a stiffness optimum at which migration is maximal. Here we present a cell migration simulator that predicts a stiffness optimum that can be shifted by altering the number of active molecular motors and clutches. This prediction is verified experimentally by comparing cell traction and F-actin retrograde flow for two cell types with differing amounts of active motors and clutches: embryonic chick forebrain neurons (ECFNs; optimum ~1 kPa) and U251 glioma cells (optimum ~100 kPa). In addition, the model predicts, and experiments confirm, that the stiffness optimum of U251 glioma cell migration, morphology, and F-actin retrograde flow rate can be shifted to lower stiffness by simultaneous drug inhibition of myosin II motors and integrin-mediated adhesions.
Publication Title
Shifting the optimal stiffness for cell migration.
Sample Metadata Fields
Sex, Cell line
View Samples