Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA Sequencing of Adamantinomatous Craniopharyngioma

ABSTRACT: RNA sequencing of 18 human ACP samples, 3 foetal pituitaries, 3 non functioning pituitary adenomas

INSTRUMENT(S): Illumina MiSeq

ORGANISM(S): Homo sapiens

SUBMITTER: John Apps

PROVIDER: E-MTAB-5267 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target.

Apps John R JR Carreno Gabriela G Gonzalez-Meljem Jose Mario JM Haston Scott S Guiho Romain R Cooper Julie E JE Manshaei Saba S Jani Nital N Hölsken Annett A Pettorini Benedetta B Beynon Robert J RJ Simpson Deborah M DM Fraser Helen C HC Hong Ying Y Hallang Shirleen S Stone Thomas J TJ Virasami Alex A Donson Andrew M AM Jones David D Aquilina Kristian K Spoudeas Helen H Joshi Abhijit R AR Grundy Richard R Storer Lisa C D LCD Korbonits Márta M Hilton David A DA Tossell Kyoko K Thavaraj Selvam S Ungless Mark A MA Gil Jesus J Buslei Rolf R Hankinson Todd T Hargrave Darren D Goding Colin C Andoniadou Cynthia L CL Brogan Paul P Jacques Thomas S TS Williams Hywel J HJ Martinez-Barbera Juan Pedro JP

Acta neuropathologica 20180314 5

Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP ...[more]

PMID: 29541918

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Project description:Pituitary adenomas cause significant endocrine and mass-related morbidity. Not much is known about mechanisms underlying pituitary tumor pathogenesis.We searched for a side population (SP) in pituitary tumor, representing cells with high efflux capacity and potentially enriching for cancer/tumor stem cells (CSC/TSC). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the further purified SP (pSP) depleted from endothelial and immune cells, enriches for cells that express ‘tumor stemness’ markers and signaling pathways, including epithelial-mesenchymal transition (EMT)-linked factors. The adenomas were found to contain self-renewing sphere-forming cells, considered a property of TSC. The sphere-initiating cells were retrieved in the pSP.Because benign pituitary adenomas do not grow in vitro and failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used. We identified a SP in this cell line and found it more tumorigenic than the main population (MP). Of the two EMT-regulatory pathways tested, inhibition of Cxcr4 signaling reduced EMT-linked cell motility in vitro as well as xenograft tumor growth, whereas activation of TGFβ had no effect.The tumor pSP showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2-/-) mice bearing prolactinomas, contain more pSP, Sox2+ and colony-forming cells than wildtype glands.In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. Our study may contribute to a better understanding of pituitary tumor pathogenesis and lead to new therapeutic targets. We determined gene expression profiles for 9 human pituitary adenoma samples (5 x NF-A; 4 x GH-A). The samples were obtained immediately after transsphenoidal resection (by the neurosurgeon Dr. van Loon, Division Neurosurgery, University Hospitals Leuven). Informed consent was received from the patients. Hormonal phenotype was determined by the Department of Imaging and Pathology (University Hospitals Leuven). For each sample, total SP and MP cells were sorted by FACS. Separate assays were run subsequently for the two fractions. As such we present data from 18 microarrays.

Dataset Information

RNA Sequencing of Adamantinomatous Craniopharyngioma

Publications

Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target.

Similar Datasets

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