Project description:Pheochromocytoma (PCC) and paraganglioma (PGL) are neuroendocrine tumours arising in the adrenal medulla and paraganglia of the autonomous nervous system, respectively. Malignant PCC/PGL are mostly caused by germline mutations of SDHB, encoding a subunit of succinate dehydrogenase. Gene expression changes associated with SDHB inactivation were investigated in a two genetically defined murine cellular models. These models were generated by Cre-mediated recombination in spontaneously immortalized mouse chromaffin cells (imCCs) and adrenal fibroblasts (MAFs).
Project description:Illumina Infinium MethylationEPIC BeadChip array files from phaeochromocytoma, paraganglioma tumours of different genotypes and normal adrenal medulla control samples. This is the first study using high-resolution MethylationEPIC arrays and also includes a large number of Cluster 1 tumours (n=16) which exhibit extensive epigenetic deregulation.
Project description:Genome wide DNA methylation profiling of pheochromocytoma/paraganglioma samples carrying different mutations. The Illumina Infinium EPIC Human DNA methylation Beadchip was used to obtain DNA methylation profiles.
Project description:Genome wide DNA methylation profiling of pheochromocytoma/paraganglioma samples carrying different mutations. The Illumina Infinium EPIC Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 850,000 CpGs. The main goal of this project was to find specific methylation profiles associated to the presence of mutations in the different genetic sub-classes of pheochromocytomas/paragangliomas.
2020-06-15 | GSE123185 | GEO
Project description:A phenotypically correct rat model for SDHB-mutated pheochromocytoma/paraganglioma
Project description:The conserved B-subunit of succinate dehydrogenase (SDH) participates in the TCA cycle and mitochondrial electron transport. The Arg230His mutation in SDHB causes heritable pheochromocytoma/paraganglioma (PPGL). In C. elegans, we generated an in vivo PPGL model (SDHB-1 Arg244His; equivalent to human Arg230His) which manifests delayed development, shortened lifespan, attenuated ATP production and reduced mitochondrial number. Although succinate is elevated in both missense and null sdhb-1(gk165) mutants, transcriptomic comparison suggests very different causal mechanisms that are supported by metabolic analysis where only Arg244His (not null) worms elevate lactate/pyruvate levels, pointing to a missense-induced, ‘Warburg’-like aberrant glycolysis. In silico predictions of the SDHA-B dimer structure demonstrate that Arg230His modifies the catalytic cleft despite the latter’s remoteness from the mutation site. We hypothesise that Arg230His SDHB mutation rewires metabolism, reminiscent of metabolic reprogramming in cancer. Our tractable model provides a novel tool to investigate the metastatic propensity of this familial cancer and our approach may illuminate wider SDH pathology.
Project description:Until now, it is nearly impossible to diagnose malignancy of pheochromocytoma/paraganglioma with pathological examinations. The aim of the study is to find the genes which can be applied as a biomarker in the clinic to distinguish benign and malignant forms of pheochromocytoma/paraganglioma.
Project description:Transcriptional analysis of 84 primary pheochromocytoma (PCC)/paraganglioma tumors. 84 samples (primary pheochromocytoma (PCC)/paraganglioma tumors) were hybridized onto a cDNA microarray in order to investigate possible heterogeneity within these tumors
Project description:Cytogenetic analysis of 36 pheochromocytoma and four paraganglioma using high density arrays A series of 36 pheochromocytoma and four paraganglioma were analysed for genomic structural alterations using high density copy number arrays
