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Methylome analysis in pituitary neuroendocrine tumors

ABSTRACT: Methylome analysis in pituitary neuroendocrine tumors

PROVIDER: PRJEB50807 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR8528880_1.fastq.gz	Fastqsanger.gz
	ERR8528880_2.fastq.gz	Fastqsanger.gz
	ERR8528890_1.fastq.gz	Fastqsanger.gz
	ERR8528890_2.fastq.gz	Fastqsanger.gz
	ERR8528881_1.fastq.gz	Fastqsanger.gz

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DNA methylation pattern in somatotroph pituitary neuroendocrine tumors

Project description:DNA methylation pattern in somatotroph pituitary neuroendocrine tumors

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Transcriptomic Profiling of Lactotroph Pituitary Neuroendocrine Tumors via RNA Sequencing and Ingenuity Pathway Analysis

Project description:Background: Lactotroph pituitary neuroendocrine tumors (PitNETs) are common pituitary tumors, but their underlying molecular mechanisms remain unclear. This study aimed to investigate the transcriptomic landscape of lactotroph PitNETs and identify potential molecular mechanisms and therapeutic targets through RNA sequencing and ingenuity pathway analysis (IPA). Methods: Lactotroph PitNET tissues from five surgical cases without dopamine agonist treatment underwent RNA sequencing. Normal pituitary tissues from three patients served as controls. Differentially expressed genes (DEGs) were identified, and the functional pathways and gene networks were explored by IPA. Results: Transcriptome analysis revealed that lactotroph PitNETs had gene expression patterns that were distinct from normal pituitary tissues. We identified 1,172 upregulated DEGs, including nine long intergenic noncoding RNAs (lincRNAs) belonging to the top 30 DEGs. IPA of the upregulated DEGs showed that the estrogen receptor signaling, oxidative phosphorylation signaling, and EIF signaling were activated. In gene network analysis, key upstream regulators, such as EGR1, PRKACA, PITX2, CREB1, and JUND, may play critical roles in lactotroph PitNETs.

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Transcriptome and methylome analysis reveal three cellular origins of pituitary tumors

Project description:Transcriptome and methylome analysis reveal three cellular origins of pituitary tumors

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Transcriptome and methylome analysis reveal three cellular origins of pituitary tumors

Project description:The pituitary tumors (PA) arise in adenohypophyseal cells and are the second most common tumor in central nervous system. Reflective of their monoclonal cell of origin these tumors could be classified according to the hormone that they produce. The mutational and copy number variation burden in these tumors are scarce, indicating other molecular events are involved in pituitary tumorigenesis. Here we show throughout transcriptome and methylome analysis that there are three readily distinctive molecular signatures. The first group is comprised by the gonadotropes, null cell and silent corticotroph PA, the second group comprised by ACTH PA and the group cluster together the TSH-, PRL- and GH- PA. These groups showed CACNA2D4, EPHA4 and SLIT1 gene up-regulation, respectively. Pathway enrichment analysis support the previous observations. The calcium signaling pathway is characteristic for gonadotropes null cell and silent corticotroph, the Renin-Angiotensin system for the ACTH PA and the Fatty acid metabolisms for the TSH-, PRL-, GH- cluster. The analysis of scRNA-seq from non-tumoral pituitary tissue revealed that these three groups originate since the pituitary development/embryogenesis. The immune cell infiltration landscape revealed that PA could be potentially infiltrated by NK and mast cells. Taken together these results correlate with the expression of the NR5A1, TBX19 and POU1F1 transcription factors, which drive pituitary embryogenesis and theoretically tumorigenesis and potentially indicates three divergent cell precursors cells. We used microarrays to detail the molecular alteration in PA compared to non-tumoral gland.

2020-11-16 | GSE147786 | GEO

Multilineage pituitary neuroendocrine tumors with PIT1/SF1 co-expression

Project description:Multilineage pituitary neuroendocrine tumors with PIT1/SF1 co-expression

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Integrating methylome and transcriptome signatures expands the molecular classification of the pituitary tumors

Project description:Abnormal DNA methylation contributes to tumor progression and is emerging as a prognostic marker in several types of cancers. Pituitary tumors (PitNETs) tumorigenesis is still not completely understood. Few studies have integrated exome, methylome, and transcriptome analyses. Taking advantage of a comprehensive phenotypic characterized Brazilian cohort, which has heterogeneous ethnic origin, we combined methylome and transcriptome analysis of the three major subtypes of surgically resectable PitNETs (n = 77): GH-secreting (acromegaly, n = 18), ACTH-secreting (Cushing disease, n = 13), and non-functioning (n = 46) PitNETs. Here, we included methylome and basal patient / tumor data.

2023-01-26 | GSE207937 | GEO

Proteogenomic Landscape and Clinical Characterization of GH-producing pituitary adenomas/ somatotroph pituitary neuroendocrine tumors

Project description:Proteogenomic Landscape and Clinical Characterization of GH-producing pituitary adenomas/ somatotroph pituitary neuroendocrine tumors

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DNA methylation pattern in somatotroph pituitary neuroendocrine tumors

Project description:Secretion of growth hormone by sporadic somatotroph neuroendocrine pituitary tumors (PitNETs) is the most common cause of acromegaly.Genome-wide DNA methylation was investigated in 48 somatotroph PitNETs with EPIC microarrays. Three subtypes of the tumors were identified. Subtype 1 tumors are densely granulated tumors without GNAS mutation characterized by high expression of NR5A1 (SF-1) and GIPR. The expression of both genes is correlated with specific methylation pattern at gene body and promoter methylation. Subtype 1 has generally lower methylation level at 5’ gene regulatory regions and CpG islands as compared to other tumor clusters. Subtype 2 are densely granulated PiNETs with common GNAS-mutations while Subtype 3 are mainly sparsely granulated tumors. Methylation/expression analysis indicate that the levels of ~50% genes differentially expressed genes between tumor subtypes that are located at in differentially methylated regions are DNA methylation dependent. These DNA methylation-controlled genes include CDKN1B, CCND2, EBF3, CDH4, CDH12 MGMT, STAT5A, PLXND1, PTPRE and MMP16 as wells as genes encoding ion channels and semaphorins. Results of DNA methylation profiling confirms three molecular subtypes of somatotroph PitNETs that differ in both gene expression and methylation pattern. High expression of NR5A1 and GIPR in subtype 1 tumors is correlated to specific methylation at both genes.

2023-09-25 | GSE226764 | GEO

Transcriptomic Profiling of Lactotroph Pituitary Neuroendocrine Tumors via RNA Sequencing and Ingenuity Pathway Analysis

Project description:Transcriptomic Profiling of Lactotroph Pituitary Neuroendocrine Tumors via RNA Sequencing and Ingenuity Pathway Analysis

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Integrating methylome and transcriptome signatures expands the molecular classification of the pituitary tumors [RNA-seq]

Project description:Pituitary tumors (PitNETs) tumorigenesis is still not completely understood. Few studies have integrated exome, methylome, and transcriptome analyses. Taking advantage of a comprehensive phenotypic characterized Brazilian cohort, which has heterogeneous ethnic origin, we combined methylome and transcriptome analysis of the three major subtypes of surgically resectable PitNETs. Here, we included RNA-seq and basal patient / tumor data of 65 PitNETs: GH-secreting (acromegaly,n = 15), ACTH-secreting (Cushing disease, n = 7), and Non-Functioning (n = 43 PitNETs).

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