Transcriptome and methylome analysis reveal three cellular origins of pituitary tumors
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ABSTRACT:
PROVIDER: PRJNA616365 | ENA |
REPOSITORIES: ENA
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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
Project description:Pituitary adenomas (PA) are the second most common intracranial tumors. These neoplasms are classified according to the hormone they produce. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. The present transcriptomic and methylomic analysis of PA revealed that they segregate into three molecular clusters according to the transcription factor driving their terminal differentiation. First cluster, driven by NR5A1, consists of clinically non-functioning PA (CNFPA), comprising gonadotrophinomas and null cell; the second cluster consists of clinically evident ACTH adenomas and silent corticotroph adenomas, driven by TBX19; and the third, POU1F1-driven TSH-, PRL- and GH-adenomas, segregated together. Genes such as CACNA2D4, EPHA4 and SLIT1, were upregulated in each of these three clusters, respectively. Pathway enrichment analysis revealed specific alterations of these clusters: calcium signaling pathway in CNFPA; renin-angiotensin system for ACTH-adenomas and fatty acid metabolism for the TSH-, PRL-, GH-cluster. Non-tumoral pituitary scRNAseq data confirmed that this clustering also occurs in normal cytodifferentiation. Deconvolution analysis identify potential mononuclear cell infiltrate in PA consists of dendritic, NK and mast cells. Our results are consistent with a divergent origin of PA, which segregate into three clusters that depend on the specific transcription factors driving late pituitary cytodifferentiation.
| S-EPMC7652879 | biostudies-literature
Project description:Methylome analysis in pituitary neuroendocrine tumors
| PRJEB50807 | ENA
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
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).
2023-01-26 | GSE209903 | GEO
Project description:Integrating methylome and transcriptome signatures expands the molecular classification of the pituitary tumors
| PRJNA857710 | ENA
Project description:Despite a considerable literature concerning the molecular pathogenesis of pituitary tumors, the mechanisms of pituitary tumors development and progression remain unknown. Four SAGE cDNA libraries were constructed using a pool of mRNA obtained from five GH-, two ACTH-secreting, and four non secreting pituitary tumors (NS), and three normal pituitaries from patients who had accidental death, using I-SAGE kit (Invitrogen). The aim of this study was to evaluate the differential gene expression profile by SAGE genes in different subtypes of pituitary tumors to contribute for understanding of pituitary tumorigenesis. Comparative analysis of gene expression profiles in subtypes of pituitary tumores.
2014-04-10 | E-GEOD-37153 | biostudies-arrayexpress
Project description:Despite a considerable literature concerning the molecular pathogenesis of pituitary tumors, the mechanisms of pituitary tumors development and progression remain unknown. Four SAGE cDNA libraries were constructed using a pool of mRNA obtained from five GH-, two ACTH-secreting, and four non secreting pituitary tumors (NS), and three normal pituitaries from patients who had accidental death, using I-SAGE kit (Invitrogen). The aim of this study was to evaluate the differential gene expression profile by SAGE genes in different subtypes of pituitary tumors to contribute for understanding of pituitary tumorigenesis.
2014-04-10 | GSE37153 | GEO
Project description:Integrating methylome and transcriptome signatures expands the molecular classification of the pituitary tumors [RNA-seq]
| PRJNA862905 | ENA
Project description:CGH array analysis was performed on 195 fresh-frozen pituitary tumors (56 gonadotroph, 11 null-cell, 56 somatotroph, 39 lactotroph and 33 corticotroph), with 5 years post-surgery follow-up
2021-01-01 | E-MTAB-9237 | biostudies-arrayexpress