Project description:Nonfunctioning pituitary adenomas (NFPAs) are among the most frequent intracranial tumors but their molecular background, including changes in epigenetic regulation, remains poorly understood. We performed genome-wide DNA methylation profiling of 34 NFPAs and normal pituitary samples. Methylation status of the selected genomic regions and expression level of corresponding genes were assessed in a group of 75 patients. NFPAs exhibited distinct global methylation profile as compared to normal pituitary. Aberrant DNA methylation appears to contribute to deregulation of the cancer-related pathways as shown by preliminary functional analysis. Promoter hypermethylation and decreased expression level of SFN, STAT5A, DUSP1, PTPRE and FGFR2 was confirmed in the enlarged group of NFPAs. Difference in the methylation profiles between invasive and non-invasive NFPAs is very slight. Nevertheless, invasiveness-related aberrant epigenetic deregulation of the particular genes was found including upregulation of ITPKB and downregulation CNKSR1 in invasive tumors.
Project description:Gonadotroph adenomas comprise 15–40 % of all pituitary tumors, are usually non-functioning and are often large and invasive at presentation. Surgery is the first-choice treatment, but complete resection is not always achieved, leading to high recurrence rates. As gonadotroph adenomas poorly respond to conventional pharmacological therapies, novel treatment strategies are needed. Their identification has been hampered by our incomplete understanding of the molecular pathogenesis of these tumors. Recently, we dem¬onstrated that MENX-affected rats develop gonadotroph adenomas closely resembling their human counterparts. To discover new genes/pathways involved in gonadotroph cells tumorigenesis, we performed transcriptome profiling of rat tumors versus normal pituitary. Adenomas showed overrep¬resentation of genes involved in cell cycle, development, cell differentiation/proliferation, and lipid metabolism. Bioinfor¬matic analysis identified downstream targets of the transcrip¬tion factor SF-1 as being up-regulated in rat (and human) adenomas. Meta-analyses demonstrated remarkable similari¬ties between gonadotroph adenomas in rats and humans, and highlighted common dysregulated genes, several of which were not previously implicated in pituitary tumorigenesis. Two such genes, CYP11A1 and NUSAP1, were analyzed in 39 human gonadotroph adenomas by qRT-PCR and found to be up-regulated in 77 and 95 % of cases, respectively. Immunohistochemistry detected high P450scc (encoded by CYP11A1) and NuSAP expression in 18 human gonado¬troph tumors. In vitro studies demonstrated for the first time that Cyp11a1 is a target of SF-1 in gonadotroph cells and promotes proliferation/survival of rat pituitary adenoma pri¬mary cells and cell lines. Our studies reveal clues about the molecular mechanisms driving rat and human gonadotroph adenomas development, and may help identify previously unexplored biomarkers for clinical use.
Project description:We collected samples from patients with invasive and non-invasive pituitary adenomas from Beijing Tiantan Hospital for protein extraction and quantitative analysis, and identified invasive differential proteins (DEPs) by differential analysis of the two groups.
Project description:Recurrent single-nucleotide and small indel somatic mutations were infrequent among the three adenoma subtypes. However, somatic copy-number alterations (SCNA) were identified in all three pituitary adenoma subtypes. Methylation analysis revealed adenoma subtype-specific DNA methylation profiles, with GHsecreting adenomas being dominated by hypomethylated sites. Likewise, gene-expression patterns revealed adenoma subtype-specific profiles. Integrating DNA methylation and gene-expression data revealed that hypomethylation of promoter regions are related with increased expression of GH1 and SSTR5 genes in GH-secreting adenomas and POMC gene in ACTH secreting adenomas. Finally, multispectral IHC staining of immune-related proteins showed abundant expression of PD-L1 among all three adenoma subtypes.
Project description:The reasons why some pituitary adenomas are fucntioning(secreting hormones) or not is not well understood. This analysis dig into the transcriptomes of secreting and non-secreting corticotropic adenomas as well as non-fucntioning gonadotropic adenomas.
Project description:Gonadotroph adenomas comprise 15M-bM-^@M-^S40 % of all pituitary tumors, are usually non-functioning and are often large and invasive at presentation. Surgery is the first-choice treatment, but complete resection is not always achieved, leading to high recurrence rates. As gonadotroph adenomas poorly respond to conventional pharmacological therapies, novel treatment strategies are needed. Their identification has been hampered by our incomplete understanding of the molecular pathogenesis of these tumors. Recently, we demM-BM-,onstrated that MENX-affected rats develop gonadotroph adenomas closely resembling their human counterparts. To discover new genes/pathways involved in gonadotroph cells tumorigenesis, we performed transcriptome profiling of rat tumors versus normal pituitary. Adenomas showed overrepM-BM-,resentation of genes involved in cell cycle, development, cell differentiation/proliferation, and lipid metabolism. BioinforM-BM-,matic analysis identified downstream targets of the transcripM-BM-,tion factor SF-1 as being up-regulated in rat (and human) adenomas. Meta-analyses demonstrated remarkable similariM-BM-,ties between gonadotroph adenomas in rats and humans, and highlighted common dysregulated genes, several of which were not previously implicated in pituitary tumorigenesis. Two such genes, CYP11A1 and NUSAP1, were analyzed in 39 human gonadotroph adenomas by qRT-PCR and found to be up-regulated in 77 and 95 % of cases, respectively. Immunohistochemistry detected high P450scc (encoded by CYP11A1) and NuSAP expression in 18 human gonadoM-BM-,troph tumors. In vitro studies demonstrated for the first time that Cyp11a1 is a target of SF-1 in gonadotroph cells and promotes proliferation/survival of rat pituitary adenoma priM-BM-,mary cells and cell lines. Our studies reveal clues about the molecular mechanisms driving rat and human gonadotroph adenomas development, and may help identify previously unexplored biomarkers for clinical use. We compared five control animals and 16 homozygous mutants (p27Kip1/Cdknb1)
Project description:This series includes the four major subtypes of pituitary adenomas and normal post-mortem pituitary tissue; Data Transformation; Using Affymetrix Microarray Suite 5.0 global scaling was applied to the quantification data to adjust the average recorded to a target intensity of 100. Data were then exported into the bioinformatics software GeneSpring 6.0 (Silicon Genetics, Redwood City, CA) for further analysis. Data normalization was performed to scale the data so that the average intensity value on each array was 1 by dividing each expression value by the median of the expression levels on each chip. The individual gene expression levels for each of the 4 pituitary adenoma subtype arrays was divided by the expression level in the normal pituitary array. Thus, the data are presented as relative to the expression in normal pituitary tissue. Filtering was then performed to identify genes over-expressed or under-expressed at least 2.0 fold in tumours compared to normal pituitary. TABLE 1:; The genes / ESTs differentially overexpressed >= 2-fold in at least one pituitary adenoma subtype compared to normal pituitary. Negative values represent underexpression. Where genes are represented by more than one probe set, individual probe data sets are given. TABLE 2:; The genes / ESTs differentially underexpressed >= 2-fold in at least one pituitary adenoma subtype compared to normal pituitary. Negative values represent underexpression. Where genes are represented by more than one probe set, individual probe data sets are given.
Project description:This dataset contains high throughput sequencing data from Non-functioning pituitary adenomas (NFPAs) together with associated control sections of healthy pituitary which was obtained from formalin-fixed paraffin embeded samples. All of the samles come from patients of Maria Sklodowska-Curie Memorial Cancer Center in Warsaw. All the samples were sequenced using Ion Torrent technology in Maria Sklodwoska-Curie Memorial Cancer Center in Warsaw. They were further processed and used to perform complex analyses using other high-throughput data.
Project description:We aimed to identify epigenetic alterations associated with the development of traditional serrated adenomas (TSAs). Through DNA methylation analysis with HumanMethylation450 BeadChip in TSAs and sessile serrated adenoma/polyp (SSA/Ps), we identified DNA methylation specifically associated with TSA development.