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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Similar gene expression profiles of sporadic, PGL2-, and SDHD-linked paragangliomas

ABSTRACT: The similarity in gene-expression profiles suggest that PGL2, like SDHD, is involved in the functionality of the SDH complex, and that tumor formation in these three subgroups involves the same pathways as in SDH linked paragangliomas. We were not able to clarify the identity of PGL2 on 11q13. The lack of differential gene-expression of chromosome 11 genes might indicate that chromosome 11 loss, as demonstrated in SDHD-linked paragangliomas, is an important feature in the formation of a paraganglioma regardless of the genetic background. Keywords: disease state analysis We compared the gene expression profiles of sporadic (n=7), SDHD- (n=6) and PGL2-linked (n=4) head and neck paraganglioma.

ORGANISM(S): Homo sapiens

SUBMITTER: Jan Oosting

PROVIDER: E-GEOD-12921 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Similar gene expression profiles of sporadic, PGL2-, and SDHD-linked paragangliomas suggest a common pathway to tumorigenesis.

Hensen Erik F EF Goeman Jelle J JJ Oosting Jan J Van der Mey Andel G L AG Hogendoorn Pancras C W PC Cremers Cor W R J CW Devilee Peter P Cornelisse Cees J CJ

BMC medical genomics 20090511

<h4>Background</h4>Paragangliomas of the head and neck are highly vascular and usually clinically benign tumors arising in the paraganglia of the autonomic nervous system. A significant number of cases (10-50%) are proven to be familial. Multiple genes encoding subunits of the mitochondrial succinate-dehydrogenase (SDH) complex are associated with hereditary paraganglioma: SDHB, SDHC and SDHD. Furthermore, a hereditary paraganglioma family has been identified with linkage to the PGL2 locus on 11 ...[more]

PMID: 19432956

Similar Datasets

Project description:The similarity in gene-expression profiles suggest that PGL2, like SDHD, is involved in the functionality of the SDH complex, and that tumor formation in these three subgroups involves the same pathways as in SDH linked paragangliomas. We were not able to clarify the identity of PGL2 on 11q13. The lack of differential gene-expression of chromosome 11 genes might indicate that chromosome 11 loss, as demonstrated in SDHD-linked paragangliomas, is an important feature in the formation of a paraganglioma regardless of the genetic background. Keywords: disease state analysis

2008-12-10 | GSE12921 | GEO

SNP data from 30 pheochromocytomas and paragangliomas.

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.

2012-03-23 | GSE32204 | GEO

Transcription profiling of pheochromocytomas and paragangliomas (188 tumor samples)

Project description:A Cartes d'Identité des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net) | Affymetrix HG-U133 Plus 2.0 : 188 tumor samples |Pheochromocytomas and paragangliomas are neuroendocrine tumors occuring in the context of inherited cancer syndromes in approximately 30% of cases, linked to germline mutations in VHL, RET, NF1, SDHA, SDHB, SDHC, SDHD, SDHAF2 or TMEM127 genes. Although progress has been made with regard to tumorigenesis mechanisms in pheochromocytoma/paraganglioma thanks to genome-wide expression studies, the question of a putative molecular distinction between VHL- and SDHx- on one hand, and RET- and NF1-related tumors on the other hand, remained to be addressed as well as the characterization of genetic events in sporadic tumors. With this purpose, 202 pheochromocytomas/paragangliomas, including 75 hereditary tumors, were investigated by expression profiling, array CGH and somatic mutation screening. The systematic characterization of somatic genetic events associated with tumor suppressor gene germline mutations in tumor tissues reveals a majority of loss of heterozygosity (LOH) but also point mutations and copy neutral LOH. Gene-expression signature defined the hereditary tumors according to their genotype. Especially, a complete sub-separation between SDHx- and VHL-related tumors was observed. Moreover, guided by the transcriptome classification and the LOH profile, somatic mutations in VHL or RET genes were identified in 14% of sporadic pheochromocytomas/paragangliomas. A genetic cause was found in 45.5% (92/202) of the large series of pheochromocytomas/paragangliomas analyzed. Regarding mutated genes, specific molecular pathways involved in tumorigenesis mechanisms are showed. Altogether, these new findings suggest that somatic mutation analysis would give important clues for personalized molecular target therapies.

2011-07-07 | E-MTAB-733 | biostudies-arrayexpress

SNP data from 30 pheochromocytomas and paragangliomas.

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.

2012-03-23 | E-GEOD-32204 | biostudies-arrayexpress

EPAS1-mutated paragangliomas are associated with hemoglobin disorders

Project description:This study reports a large series patients presenting EPAS1-mutated paraganglioma in whom we investigated a cause underlying chronic hypoxia. Four patients (10%) suffered from hypoxemic heart disease. In patients with available hemoglobin electrophoresis results, 59% presented a hemoglobin disorder. Histological and transcriptomic characterization of EPAS1-tumors revealed increased angiogenesis and high similarities with pseudohypoxic paragangliomas caused by VHL gene mutations.

2023-12-11 | GSE249273 | GEO

Expression Profiling of pheochromocytomas of various genetic origins

Project description:Pheochromocytomas are neural crest-derived tumors that arise from inherited or sporadic mutations in at least six independent genes: RET, VHL, NF1, and subunits B, C and D of succinate dehydrogenase (SDH). The proteins encoded by these multiple genes regulate distinct functions. To identify molecular interactions between the distinct pathways we performed expression profiling of a large cohort of pheochromocytomas. We show here a functional link between tumors with VHL mutations and those with disruption of the genes encoding for succinate dehydrogenase (SDH) subunits B (SDHB) and D (SDHD). A transcription profile of reduced oxidoreductase is detected in all three of these tumor types, together with an angiogenesis/hypoxia profile typical of VHL dysfunction. The oxidoreductase defect, not previously detected in VHL-null tumors, is explained by suppression of the SDHB protein, a component of mitochondrial complex II. The decrease in SDHB is also noted in tumors with SDHD mutations. Gain-of-function and loss-of-function analyses show that the link between hypoxia signals (via VHL) and mitochondrial signals (via SDH) is mediated by HIF1?. These findings explain the shared features of pheochromocytomas with VHL and SDH mutations and suggest an additional mechanism for increased HIF1? activity in tumors. Keywords: disease state analysis: Primary sporadic and hereditary pheochromocytomas and paragangliomas

2005-08-12 | GSE2841 | GEO

High-density genome-wide copy number variation (CNV) in human head and neck paragangliomas.

Project description:Gene-centric CNV analysis of 24 individual paraganglioma cases identified a list of 104 genes most significantly targeted by tumor-associated alterations. The NOTCH signaling pathway was the most significantly enriched term in the list. Overexpression of the relevant NOTCH pathway proteins in sustentacular (glial), chief (neuroendocrine) and endothelial cells was confirmed by immunomorphological studies in 47 paragangliomas, including CNV-tested cases. NOTCH upregulation was observed also in cases with no evidence of CNVs at NOTCH signaling genes, suggesting altered epigenetic modulation of the pathway. Notably, this was confirmed by microRNA expression analysis, that showed tumor-associated downregulation of the miR-200s and miR-34s families, correlated to NOTCH signaling and directly targeting NOTCH1. Total DNA from paraganglioma sample compared to total DNA from paired blood sample.

2013-08-21 | E-GEOD-49614 | biostudies-arrayexpress

Investigation of post-translational histone modifications in pheochromocytomas and paragangliomas

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.

2024-01-26 | PXD025689 | Pride

High-density genome-wide copy number variation (CNV) in human head and neck paragangliomas.

2013-08-21 | GSE49614 | GEO