AUTHOR=Xu Yiwen , Niu Yamei , Deng Kan , Pan Hui , Feng Feng , Gong Fengying , Tong Wei-Min , Chen Shi , Lu Lin , Wang Renzhi , You Hui , Yao Yong , Zhu Huijuan 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00361

DOI=10.3389/fendo.2020.00361

ISSN=1664-2392

ABSTRACT=<p>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 <italic>TET2</italic> 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‰), <italic>P</italic> &lt; 0.0001). There was positive correlation of 5hmC levels with TET2 total and nuclear expression in NFPAs (<italic>r</italic> = 0.461, <italic>P</italic> = 0.018; <italic>r</italic> = 0.458, <italic>P</italic> = 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‰, <italic>P</italic> = 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 <italic>TET2</italic> mutation.</p>