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Genome-scale methylome profiling of human pheochromocytomas and paragangliomas (Illumina methylation beadchips) and mouse chromaffin cells (RRBS)

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE43298 | GEO | 2013/05/06

SECONDARY ACCESSION(S): PRJNA185310

REPOSITORIES: GEO

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Genome-scale methylome profiling of human pheochromocytomas and paragangliomas (Illumina methylation beadchips) and mouse chromaffin cells (RRBS)

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-05-06 | E-GEOD-43298 | biostudies-arrayexpress

Genome-scale methylome profiling of pheochromocytomas and paragangliomas with Illumina HumanMethylation450 arrays

Project description:Genome-scale DNA methylation was analyzed in a cohort of paragangliomas to identify DNA methylation changes.

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Genome-scale methylome profiling of pheochromocytomas and paragangliomas with Illumina Infinium 27k Human Methylation arrays

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Genome-scale methylome profiling of pheochromocytomas and paragangliomas with Illumina Infinium 27k Human Methylation arrays

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.

2013-05-06 | E-GEOD-39198 | biostudies-arrayexpress

Genome-scale methylome profiling of pheochromocytomas and paragangliomas with Illumina HumanMethylation450 arrays

Project description: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.

2013-05-06 | E-GEOD-43293 | biostudies-arrayexpress

ChAMP: updated methylation analysis pipeline for Illumina BeadChips.

Project description:SummaryThe Illumina Infinium HumanMethylationEPIC BeadChip is the new platform for high-throughput DNA methylation analysis, effectively doubling the coverage compared to the older 450 K array. Here we present a significantly updated and improved version of the Bioconductor package ChAMP, which can be used to analyze EPIC and 450k data. Many enhanced functionalities have been added, including correction for cell-type heterogeneity, network analysis and a series of interactive graphical user interfaces.Availability and implementationChAMP is a BioC package available from https://bioconductor.org/packages/release/bioc/html/ChAMP.html.Contacta.teschendorff@ucl.ac.uk or s.beck@ucl.ac.uk or a.feber@ucl.ac.uk.Supplementary informationSupplementary data are available at Bioinformatics online.

| S-EPMC5860089 | biostudies-literature

Molecular Alterations in Dog Pheochromocytomas and Paragangliomas.

Project description:8658860258318000Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (SDHB and SDHD) were identified in pet dogs that presented with spontaneously arising pheochromocytomas (PCC) and paragangliomas (PGL; together PPGL), suggesting dogs might be an interesting comparative model for the study of human PPGL. To study whether canine PPGL resembled human PPGL, we investigated a series of 50 canine PPGLs by immunohistochemistry to determine the expression of synaptophysin (SYP), tyrosine hydroxylase (TH) and succinate dehydrogenase subunit A (SDHA) and B (SDHB). In parallel, 25 canine PPGLs were screened for mutations in SDHB and SDHD by Sanger sequencing. To detect large chromosomal alterations, single nucleotide polymorphism (SNP) arrays were performed for 11 PPGLs, including cases for which fresh frozen tissue was available. The immunohistochemical markers stained positive in the majority of canine PPGLs. Genetic screening of the canine tumors revealed the previously described variants in four cases; SDHB p.Arg38Gln (n = 1) and SDHD p.Lys122Arg (n = 3). Furthermore, the SNP arrays revealed large chromosomal alterations of which the loss of chromosome 5, partly homologous to human chromosome 1p and chromosome 11, was the most frequent finding (100% of the six cases with chromosomal alterations). In conclusion, canine and human PPGLs show similar genomic alterations, suggestive of common interspecies PPGL-related pathways.

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The correlation of methylation levels measured using Illumina 450K and EPIC BeadChips in blood samples.

Project description:AimWe examined concordance of methylation levels across the Illumina Infinium HumanMethylation450 BeadChip and the Infinium MethylationEPIC BeadChip.MethodsWe computed the correlation for 145 whole blood DNA samples at each of the 422,524 CpG sites measured by both chips.ResultsThe correlation at some sites was high (up to r = 0.95), but many sites had low correlation (55% had r < 0.20). The low correspondence between 450K and EPIC measured methylation values at many loci was largely due to the low variability in methylation values for the majority of the CpG sites in blood.ConclusionFiltering out probes based on the observed correlation or low variability may increase reproducibility of BeadChip-based epidemiological studies.

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Pheochromocytomas and Paragangliomas: From Genetic Diversity to Targeted Therapies.

Project description:Pheochromocytoma and paraganglioma (PCPGs) are rare neuroendocrine tumors that arise from the chromaffin tissue of adrenal medulla and sympathetic ganglia. Although metastatic PCPGs account for only 10% of clinical cases, morbidity and mortality are high because of the uncontrollable mass effect and catecholamine level generated by these tumors. Despite our expanding knowledge of PCPG genetics, the clinical options to effectively suppress PCPG progression remain limited. Several recent translational studies revealed that PCPGs with different molecular subtypes exhibit distinctive oncogenic pathways and spectrum of therapy resistance. This suggests that therapeutics can be adjusted based on the signature molecular and metabolic pathways of PCPGs. In this review, we summarized the latest findings on PCPG genetics, novel therapeutic targets, and perspectives for future personalized medicine.

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Genetics of Pheochromocytomas and Paragangliomas Determine the Therapeutical Approach.

Project description:Pheochromocytomas and paragangliomas are the most heritable endocrine tumors. In addition to the inherited mutation other driver mutations have also been identified in tumor tissues. All these genetic alterations are clustered in distinct groups which determine the pathomechanisms. Most of these tumors are benign and their surgical removal will resolve patient management. However, 5-15% of them are malignant and therapeutical possibilities for them are limited. This review provides a brief insight about the tumorigenesis associated with pheochromocytomas/paragangliomas in order to present them as potential therapeutical targets.

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