Similar gene expression profiles of sporadic, PGL2-, and SDHD-linked paragangliomas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE12921 | GEO | 2008/12/10
SECONDARY ACCESSION(S): PRJNA110835
REPOSITORIES: GEO
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 We compared the gene expression profiles of sporadic (n=7), SDHD- (n=6) and PGL2-linked (n=4) head and neck paraganglioma.
2008-12-10 | E-GEOD-12921 | biostudies-arrayexpress
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
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
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
Project description:Several mechanisms have been proposed to account for Sdh-mutation-induced tumorigenesis, the most accepted of which is based on the constitutive expression of the hypoxia-inducible factor 1alpha (Hif1alpha) at normal oxygen tension, a theory referred to as pseudo-hypoxic drive. Other molecular processes, such as oxidative stress, apoptosis or chromatin remodeling have been also proposed to play a causative role. Nevertheless, the actual contribution of each of these mechanisms has not been definitively established. Moreover, the biological factors that determine the tissue-specificity of these tumors have not been identified. In this work, we made use of the inducible SDHD-ESR mouse, a conditional mutant in the SdhD gene, which encodes the small subunit of MCII, and that acts as a tumor suppressor gene in humans. We performed microarray analysis of kidney in order to identify other early gene expression changes elicited by SdhD deletion.
2013-11-15 | GSE52196 | GEO
Project description:Several mechanisms have been proposed to account for Sdh-mutation-induced tumorigenesis, the most accepted of which is based on the constitutive expression of the hypoxia-inducible factor 1alpha (Hif1alpha) at normal oxygen tension, a theory referred to as pseudo-hypoxic drive. Other molecular processes, such as oxidative stress, apoptosis or chromatin remodeling have been also proposed to play a causative role. Nevertheless, the actual contribution of each of these mechanisms has not been definitively established. Moreover, the biological factors that determine the tissue-specificity of these tumors have not been identified. In this work, we made use of the inducible SDHD-ESR mouse, a conditional mutant in the SdhD gene, which encodes the small subunit of MCII, and that acts as a tumor suppressor gene in humans. We performed microarray analysis of kidney in order to identify other early gene expression changes elicited by SdhD deletion. 8 samples from heterozygous (+/-) and 8 samples from null mutants (SDHD-ESR), paired by two and hybrydized against a pool of 8 samples from homozygous wt (+/+) animals.
2013-11-15 | E-GEOD-52196 | biostudies-arrayexpress
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
Project description:Several mechanisms have been proposed to account for Sdh-mutation-induced tumorigenesis, the most accepted of which is based on the constitutive expression of the hypoxia-inducible factor 1alpha (Hif1alpha) at normal oxygen tension, a theory referred to as pseudo-hypoxic drive. Other molecular processes, such as oxidative stress, apoptosis or chromatin remodeling have been also proposed to play a causative role. Nevertheless, the actual contribution of each of these mechanisms has not been definitively established. Moreover, the biological factors that determine the tissue-specificity of these tumors have not been identified. In this work, we made use of the inducible SDHD-ESR mouse, a conditional mutant in the SdhD gene, which encodes the small subunit of MCII, and that acts as a tumor suppressor gene in humans. We performed microarray analysis of adrenal medulla (AM) in order to identify other early gene expression changes elicited by SdhD deletion.
2013-11-15 | GSE52195 | GEO
Project description:Several mechanisms have been proposed to account for Sdh-mutation-induced tumorigenesis, the most accepted of which is based on the constitutive expression of the hypoxia-inducible factor 1alpha (Hif1alpha) at normal oxygen tension, a theory referred to as pseudo-hypoxic drive. Other molecular processes, such as oxidative stress, apoptosis or chromatin remodeling have been also proposed to play a causative role. Nevertheless, the actual contribution of each of these mechanisms has not been definitively established. Moreover, the biological factors that determine the tissue-specificity of these tumors have not been identified. In this work, we made use of the inducible SDHD-ESR mouse, a conditional mutant in the SdhD gene, which encodes the small subunit of MCII, and that acts as a tumor suppressor gene in humans. We performed microarray analysis of adrenal medulla (AM) in order to identify other early gene expression changes elicited by SdhD deletion. 8 samples from heterozygous (+/-) and 8 samples from null mutants (SDHD-ESR), paired by two and hybrydized against a pool of 8 samples from homozygous wt (+/+) animals.
2013-11-15 | E-GEOD-52195 | biostudies-arrayexpress
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