Dataset Information

Changes in DNA 5-Hydroxymethylcytosine Levels and the Underlying Mechanism in Non-functioning Pituitary Adenomas.

ABSTRACT: Epigenetic factors have been proven to contribute to pituitary adenoma formation. 5-hydroxymethylcytosine (5hmC), which is catalyzed by ten-eleven translocation 2 (TET2), is related to DNA demethylation. In order to explore the pathogenesis of non-functioning pituitary adenomas (NFPAs), we detected genomic 5hmC levels in 57 NFPAs and 5 normal pituitary glands, and TET2 expression, distribution and TET2 alteration. Genomic 5hmC levels in NFPAs were significantly lower than those in normal pituitary glands (0.38‰ (0.24‰, 0.61‰) vs. 2.47‰ (1.56‰, 2.83‰), P < 0.0001). There was positive correlation of 5hmC levels with TET2 total and nuclear expression in NFPAs (r = 0.461, P = 0.018; r = 0.458, P = 0.019). Genomic 5hmC levels in NFPAs with TET2 p.P29R were significantly lower than those in wild type NFPAs (0.33 ± 0.18‰ vs. 0.51 ± 0.25‰, P = 0.021). We found genomic 5hmC loss in human NFPAs for the first time. Genomic 5hmC levels may be affected by TET2 expression, subcellular localization and TET2 mutation.

SUBMITTER: Xu Y

PROVIDER: S-EPMC7381329 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Changes in DNA 5-Hydroxymethylcytosine Levels and the Underlying Mechanism in Non-functioning Pituitary Adenomas.

Xu Yiwen Y Niu Yamei Y Deng Kan K Pan Hui H Feng Feng F Gong Fengying F Tong Wei-Min WM Chen Shi S Lu Lin L Wang Renzhi R You Hui H Yao Yong Y Zhu Huijuan H

Frontiers in endocrinology 20200708

Epigenetic factors have been proven to contribute to pituitary adenoma formation. 5-hydroxymethylcytosine (5hmC), which is catalyzed by ten-eleven translocation 2 (TET2), is related to DNA demethylation. In order to explore the pathogenesis of non-functioning pituitary adenomas (NFPAs), we detected genomic 5hmC levels in 57 NFPAs and 5 normal pituitary glands, and TET2 expression, distribution and <i>TET2</i> alteration. Genomic 5hmC levels in NFPAs were significantly lower than those in normal ...[more]

PMID: 32774324

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Project description:Context : Non Functioning Pituitary Adenomas (NFPAs), although typically benign, may be locally invasive. Few datas are currently available related to the molecular process of invasion in sporadic pituitary adenomas. Markers of invasiveness, important for helping the clinician in the therapeutic strategy particularly in the decision for adjuvant radiotherapy, are currently lacking. Objective: Evaluate if invasive NFPAs display a specific expression profile compared with non invasive tumors. Methods: To address this issue, we selected 40 NFPAs (38 of the gonadotroph type) and classified them as invasive (n=22) or non invasive (n=18) on the basis of MRI and surgical findings. Then we performed pangenomic analysis based on Agilent Human Whole genome Gene Expression oligonucleotide microarray (44k) Expression in order to identify genes differentially expressed between invasive and non invasive NFPA. Experiements are made in dual color with tumor samples labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3.The expressions of some genes identified by microarray screening were confirmed by real-time quantitative RT-PCR. The selection of genes was made on the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors. Moreover, some genes of interest already described in the literature were added to the analysis. Results: Prediction class analysis showed that 346 genes discriminated between invasive and non invasive NFPAs (p<0.001); 233 were up- and 113 were down-regulated between the two groups. We then tested On the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors, a set of eight genes, including MYO5A, IGFBP5, FLT3, NFE2L1, PTTG, MMP9, NCAM and NR1H3, was tested in quantitative PCR analysis and. Results confirmed those obtained in microarrays results.analysis. At the protein level, Myosin 5A (MYO5A) demonstrated stronger immunostaining in invasive NFPAs compared to non invasive NFPAs. Conclusions: We propose a molecular signature of eight genes of grossly invasive NFPAs as compared with non invasive tumors: The product of one of these genes, MYO5A, may be a useful marker of invasive process in tumoral specimens. The role of these genes in the invasiveness process and as prognostic markers of pituitary adenomas needs to be confirmedinvestigated. Method: Microarray analyses the transcriptome of 22 invasive Non Functional Pituitary Adenomas (NFPAs) and 18 non invasive NFPAs in dual color (each sample labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3).

Dataset Information

Changes in DNA 5-Hydroxymethylcytosine Levels and the Underlying Mechanism in Non-functioning Pituitary Adenomas.

Publications

Changes in DNA 5-Hydroxymethylcytosine Levels and the Underlying Mechanism in Non-functioning Pituitary Adenomas.

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