Changes in DNA 5-Hydroxymethylcytosine Levels and the Underlying Mechanism in Nonfunctioning Pituitary Adenomas

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 nonfunctioning pituitary adenomas (NFPAs), we detected genomic 5hmC levels and TET2 expression, distribution and TET2 alteration in NFPAs and normal pituitary glands. 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.

表观遗传因子已被证实可促进垂体腺瘤的形成。由十-十一易位酶2（ten-eleven translocation 2，TET2）催化产生的5-羟甲基胞嘧啶（5-hydroxymethylcytosine，5hmC）与DNA去甲基化过程相关。为探究无功能垂体腺瘤（nonfunctioning pituitary adenomas，NFPAs）的发病机制，本研究检测了NFPAs及正常垂体组织中的基因组5hmC水平、TET2的表达与分布情况，以及TET2的变异状态。本研究首次在人类NFPAs中观测到基因组5hmC缺失现象。基因组5hmC水平可能受到TET2表达、亚细胞定位以及TET2突变的影响。