Genome-scale methylome profiling of pheochromocytomas and paragangliomas with Illumina HumanMethylation450 arrays
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ABSTRACT: Genome-scale DNA methylation was analyzed in a cohort of paragangliomas to identify DNA methylation changes. Bisulfite converted DNA from 22 fresh frozen paragangliomas and 2 normal adrenal medulla samples were hybridized to Illumina HumanMethylation450 BeadChips.
Project description:Genome-scale DNA methylation was analyzed in a large cohort of pheochromocytomas and paragangliomas (PCC/PGL). Consensus clustering identified 3 stable clusters significantly associated with expression subgroups, gene mutations, and clinical parameters. Bisulfite-converted DNA from 145 fresh frozen PCC/PGL and 3 normal adrenal medulla samples were hybridized to Illumina Infinium 27k Human Methylation BeadChips.
Project description:SNP profiles from 78 pheochromocytomas and paragangliomas were analyzed to detect copy number changes and LOH. 78 pheochromocytomas and paragangliomas were analyzed with Illumina Human610-Quad v1.0 BeadChips.
Project description:SNP profiles from 30 pheochromocytomas and paragangliomas were analyzed to detect identical-by-descent haplotypes, highlighting a founder mutation of SDHD in two samples. 30 pheochromocytomas and paragangliomas were analyzed with Illumina Human610-Quad v1.0 BeadChips.
Project description:Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumours affecting a range of body sites and have the highest degree of heritability of any cancer type. SDHA, SDHB, SDHC, SDHD and SDHAF2 (collectively SDHx) code for subunits of succinate dehydrogenase, an enzyme complex in the tricarboxylic cycle that converts succinate to fumarate. Mutations in all SDHx genes play a role in PPGL pathogenesis and completely abolish succinate dehydrogenase enzymatic activity causing intracellular accumulation of oncometabolites which competitively inhibit 2-oxoglutarate-dependent oxygenases. This is a family of enzymes includes TET DNA demethylases and Jumonji C (JmjC) domain-containing histone demethylates. We and others have found that the inhibition of DNA demethylation leads to profound global DNA hypermethylation which influences expression of genes responsible for important clinical characteristics of these tumours but cannot explain the full spectrum of transcriptomic changes. We profiled histone PMTs to complement DNA methylation data and fully characterise the epigenome of these tumours.
Project description:Genome-scale DNA methylation was analyzed in a large cohort of pheochromocytomas and paragangliomas (PCC/PGL). Consensus clustering identified 3 stable clusters significantly associated with expression subgroups, gene mutations, and clinical parameters.
Project description:SNP profiles from 30 pheochromocytomas and paragangliomas were analyzed to detect identical-by-descent haplotypes, highlighting a founder mutation of SDHD in two samples.
Project description:Genome-scale DNA methylation was analyzed in a cohort of ACC and ACA to identify DNA methylation changes. Bisulfite converted DNA from 51 fresh frozen ACC and 30 ACA samples were hybridized to Illumina HumanMethylation27 BeadChips.