Project description:Transcriptom analysis of microdissect adrenal medulla after 8 weeks of cardiac pressure overload caused by transverse aortic constriction. Comparative transcriptome analysis was determined using the GeneChip Mouse Genome 430 2.0 Array (Affymetrix, Santa Clara, CA, USA). Six microarrays from microdissected adrenal medulla of mice were performed 8 weeks after transverse aortic constriction or sham operation.
Project description:Single-cell RNA sequencing of two human adrenal glands (obtained from renal cell carcinoma and pheochromocytoma cases) was performed to characterize the gene expression profile of aldosterone-producing cell clusters.
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.
Project description:In order to identify new proteins with a potential to become targets for therapy or tumor imaging in pheochromocytoma and paraganglioma, we performed detailed proteomic analysis of 22 well-characterized human PPGL samples and normal chromaffin tissue from adrenal medulla. A standard quantitative proteomic analysis of tumor tissue was accompanied by specific membrane proteome-aimed methods, namely glycopeptide capture using lectin-affinity (Zielinska 2010) or hydrazide chemistry (Tian 2007) and enrichment of membrane-embedded hydrophobic transmembrane segment (Vit et al 2016 ). The parallel application of these complementary methods recently presented as “Pitchfork strategy”, enables deep quantitative profiling of human membrane proteomes without sacrificing the information on soluble non-membrane proteins (Vit et al 2019).
Project description:Cytogenetic analysis of 36 pheochromocytoma and four paraganglioma using high density arrays A series of 36 pheochromocytoma and four paraganglioma were analysed for genomic structural alterations using high density copy number arrays
Project description:Genotype specific differences in expression profiles have been evaluated using human HuGene1.0-ST Gene Chips. In this dataset we include expression data obtained from 8 normal adrenal medulla and 45 PHEOs/PGLs patient samples. Viable appearing tissue from the center of the lesions was collected and snap frozen for RNA extraction. Each of the 45 PHEO/PGL samples was examined by pathologist upon resection. Patients PKh_27 and PKh_28 with SDHB mutation were from the same patient with samples taken from two different locations at different times. Diagnosis of PHEO/PGL has been confired in all cases histopathologically. The tissues were grouped according to genetic/syndromic background and tumor location into SDHB (n = 18), SDHD-A/T (n = 6), SDHD-HN (n= 8), and VHL (n = 13). Microarray analysis was performed on normal and tumor samples. We used PAM model to identify minimum subset of genes selective for each mutation class. Heirarchical cluster analysis was used to identify samples with similar expression patterns. Data was validated using qRT-PCR analysis.
Project description:Until now, it is nearly impossible to diagnose malignancy of pheochromocytoma/paraganglioma with pathological examinations. The aim of the study is to find the genes which can be applied as a biomarker in the clinic to distinguish benign and malignant forms of pheochromocytoma/paraganglioma.
Project description:MENX is a rat multiple endocrine neoplasia syndrome caused by a homozygous mutation of the Cdkn1b gene, encoding p27Kip1. Affected rats develop adrenomedullary hyperplasia which progresses to pheochromocytoma with time (incidence 100%), and to extra-adrenal pheochromocytoma (paraganglioma) (68%). We here report that hyperplasia and tumor have similar gene expression profiles, suggesting an early determination of the tumorigenic signature. Overexpressed genes in rat adrenal lesions are especially enriched in development/differentiation-associated genes.