DNA Methylation in Paraganglioma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE62231 | GEO | 2015/12/25
SECONDARY ACCESSION(S): PRJNA263519
REPOSITORIES: GEO
Similar Datasets
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net):we explored DNA methylation patterns associated with PPGL malignancy using two large and well characterized cohorts of PPGL collected through a multi-institutional collaboration through the European Network for the Study of Adrenal Tumors (ENS@T). Bisulfite converted DNA from fresh frozen paragangliomas and adrenal medulla samples were hybridized to Illumina Infinium 27k Human Methylation
2015-05-11 | E-GEOD-62082 | biostudies-arrayexpress
Project description:Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors arising from the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia, respectively. Local invasion, concurrent disorders, and in rare occasions metastases prevent surgical removal, which is the most effective treatment to date. Given the current lack of effective medical treatment, there is a need for novel therapeutic strategies. To identify druggable pathways driving PPGL development, we performed RNA sequencing on PPGLs (n=19) and normal adrenal medullas (NAMs; n=10) of dogs. Principal component analysis (PCA) revealed that PPGLs clearly clustered apart from NAMs. In total, 4,218 genes were differentially expressed between PPGLs and NAMs with a false discovery rate (FDR)-adjusted P value <0.05. Of these, 232 had a log2 fold change of >3 or <-3, of which 149 were upregulated in PPGLs, and 83 were downregulated. Compared with NAMs, PPGLs had increased expression of genes related to the cell cycle, tumor development, progression and metastasis, hypoxia and angiogenesis, and the Wnt signaling pathway, and decreased expression of genes related to adrenal steroidogenesis. Our data revealed several overexpressed genes that could provide targets for novel therapeutics, such as Ret Proto-Oncogene (RET), Dopamine Receptor D2 (DRD2), and Secreted Frizzled Related Protein 2 (SFRP2). Based on the PCA, PPGLs were classified into 2 groups, of which group 1 had significantly higher Ki67 scores (P=0.035) and worse survival times (P=0.04) than group 2. One of the differentially expressed genes (FDR-adjusted P value <0.1) between PPGL group 1 and 2, pleiotrophin (PTN), was significantly associated with survival (P=0.025).
2023-08-14 | GSE223526 | GEO
Project description:Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine, usually benign tumors. Currently, for these neoplasms the only reliable criterion of malignancy is the presence of metastases. The aim of the present study was to identify molecular markers that can distinguish malignant from benign PPGL. An mRNA expression array was performed on 40 benign and 11 malignant PPGL. Genes showing a significantly different expression between benign and malignant PPGL with a ratio ? 4 were selected. Differentially expressed genes were confirmed by qRT-PCR and subsequently tested in an independent validation series (4 benign and 4 malignant) by qRT-PCR. Finally, immunohistochemistry was performed for the validated genes on Tissue Micro Arrays, which included 100 PPGL (87 benign and 13 malignant). Ten genes, which were significantly differentially expressed between benign and malignant tumors (False Discovery Rates <0.05), were selected from the mRNA expression array data. Differential expression of Interleukin 13 Receptor Alpha 2 and Contactin 4 was confirmed (p<0.05) and validated by qRT-PCR. However, at the protein level, only Contactin 4 appeared to be significantly overexpressed in malignant tumors (58% in malignant versus 17% in benign; p<0.05). No difference in the immunohistochemical staining for Interleukin 13 Receptor Alpha 2 was observed between benign and malignant PPGL. Contactin 4 expression appears to be associated with malignancy in pheochromocytomas and paragangliomas, and may be predictive of malignant behavior.
2015-03-20 | GSE67066 | GEO
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net):we explored DNA methylation patterns associated with PPGL malignancy using two large and well characterized cohorts of PPGL collected through a multi-institutional collaboration through the European Network for the Study of Adrenal Tumors (ENS@T).
2015-05-11 | GSE62082 | GEO
Project description:19 non-metastatic breast cancers (controls) and 19 breast cancers showing metastases or metastatic relapse within 5 years (cases) were extracted from a multi-institutional case series of 123 breast cancer patients . Cases and controls were analyzed for DNA methylation over 56 genes by the MethDet assay [1]using a dedicated microarray (MethDet56). 1. Levenson VV, Melnikov AA: The MethDet: a technology for biomarker development. Expert Rev Mol Diagn 2011, 11:807-812.
2015-03-20 | E-MTAB-3153 | biostudies-arrayexpress
Project description:Using stable cell lines, we found that succinylation levels were highly dependent on DLST. Furthermore, PPGL-causing DLST mutations, predicted to alter DLST homo-oligomeric complex structure, caused a significant remodeling of the cellular succinylome. Succinylation is thought to cause major chemical and structural changes in proteins, most likely influencing their function. Accordingly, we found that the dysregulation of succinylation appeared to influence several essential pathways related to PPGL development such as hypoxia, glycolysis and oxidative phosphorylation. This study points to succinylation as a new mechanism involved in the development of PPGLs, supporting the growing body of research highlighting the role of this PTM in different types of cancer.
2023-05-04 | PXD036782 | Pride
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.
2020-10-01 | GSE158836 | GEO
Project description:Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status.Immunohistochemistry and mRNA expression analysis in 30 primary PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic tumor cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmatic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a PGL case harboring a MYO5B:p.G1611S mutation. Mutation analysis of additional PPGL tumors revealed additional, and hence recurrent, mutations in the paralog MYO5A. Three missense mutations in MYO5B were functionally studied using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293 cell line). Functional analysis of the mutants verified a significant increased proliferation rate in all MYO5B mutated clones (p.L587P, p.G1611S, and p.R1641C). The two somatically derived mutations p.L587P and p.G1611S were also found to increase the migration rate, and all three mutants affected intracellular transport by increased transferrin uptake. Downstream expression analysis of MYO5B mutants demonstrated a transcriptional activation of genes involved in glucose metabolism, proliferation, homeostasis, and migration. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved the malignant progression of PPGL tumors.
| EGAS00001003991 | EGA
Project description:We performed an expression profiling study of 168 primary breast tumors, lymph node metastases, and autopsy samples of primary breast tumours and metastases to liver, chest wall, lymph node, lung, and spleen, as well as positive and negative RNA controls, with technical replicates, to assess quality control methodology and probe-level reproducibility of the Illumina DASL microarray assay. The experiment included both Illumina DASL HumanRef-v3 and DASL HT-12; this series includes only the 120 HumanRef-v3 samples .
2012-10-02 | GSE32489 | GEO
Project description:We performed an expression profiling study of 168 primary breast tumors, lymph node metastases, and autopsy samples of primary breast tumours and metastases to liver, chest wall, lymph node, lung, and spleen, as well as positive and negative RNA controls, with technical replicates, to assess quality control methodology and probe-level reproducibility of the Illumina DASL microarray assay. The experiment included both Illumina DASL HumanRef-v3 and DASL HT-12; this series includes only the 48 HT12 samples .
2012-10-02 | GSE32488 | GEO