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USP8 mutations determine genes’ expression profile of pituitary corticotroph adenomas, regardless of tumor functional status.

ABSTRACT: The aim of the study was to compare genes’ expression profiles of functioning and silent corticotroph adenomas to investigate possible biological mechanism of different hormone secretion . Since USP8 is the best know driver gene mutated in large proportion of ACTH-omas we intended to verify whether the mutation occurs in SCAs and how it affects transcriptomic profile.

ORGANISM(S): Homo sapiens

PROVIDER: GSE132982 | GEO | 2019/06/20

REPOSITORIES: GEO

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Project description:Background Micro RNAs (miRNAs) are a class of small non-coding RNAs that are involved in post transcriptional gene expression regulation. miRNAS can be found in various bodily fluids including plasma. Recently circulating plasma miRNAs have been studied as biomarkers in various tumors including pituitary neuroendocrine tumors (PitNETs). However the identification of PitNET derived miRNAs in plasma remains a challenging task due to tumor volume, mass and miRNA dilution within blood. To our knowledge this is the first study that has used the NGS approach to characterize circulating miRNAs in plasma acquired from Bilateral petrosal sinus sampling (BIPSS) - a gold standard in diagnosis of ACTH secreting PitNETs. Results We sequenced plasma samples that were acquired from sinistral and dextral sides of sinus petrosus inferior and complementary plasma from peripheral venous blood (PVB). BIPSS samples were collected in three separate time periods: before administration of corticotropin releasing hormone (CRH), 5 minutes after stimulation and 15 minutes after stimulation with CRH. The highest amount of differentially expressed miRNAs was observed 5 minutes after CRH stimulation (20 upregulated, 14 downregulated). During the BIPSS procedure the highest amount of ACTH was released in the sinistral side during the 5th minute after the stimulation by CRH. In the plasma of sinistral side at the 5th minute we identified two miRNAs: hsa-miR-7-5p and hsa-miR-375-3p that were highly upregulated compared to other BIPSS samples and samples from PVB. Using clustering analysis we were able to distinguish plasma samples acquired from BIPSS from PVB plasma, indicating that the miRNA fraction characterized in this study has potentially PitNET borne origin. Conclusions In this study we provided the first insight into the landscape of circulating miRNAs in close proximity to the ACTH secreting PitNET. The data indicates that ACTH secreting PitNET releases two circulating miRNAs upon stimulation with CRH (hsa-mir-7-5p, hsa-mir-375-3p) alongside with ACTH implying the further studies of these miRNA as diagnostic markers.

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USP8 mutations determine genes’ expression profile of pituitary corticotroph adenomas, regardless of tumor functional status.

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