非功能性垂体腺瘤中的 DNA 甲基化分析。

DNA methylation profiling in nonfunctioning pituitary adenomas.

机构信息

Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.

Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland; Faculty of Mathematics, Informatics and Mechanics, University of Warsaw, Warsaw, Poland.

出版信息

Mol Cell Endocrinol. 2018 Sep 15;473:194-204. doi: 10.1016/j.mce.2018.01.020. Epub 2018 Feb 1.

DOI:10.1016/j.mce.2018.01.020

PMID:29410024

Abstract

Nonfunctioning pituitary adenomas (NFPAs) are among the most frequent intracranial tumors but their molecular background, including changes in epigenetic regulation, remains poorly understood. We performed genome-wide DNA methylation profiling of 34 NFPAs and normal pituitary samples. Methylation status of the selected genomic regions and expression level of corresponding genes were assessed in a group of 75 patients. NFPAs exhibited distinct global methylation profile as compared to normal pituitary. Aberrant DNA methylation appears to contribute to deregulation of the cancer-related pathways as shown by preliminary functional analysis. Promoter hypermethylation and decreased expression level of SFN, STAT5A, DUSP1, PTPRE and FGFR2 was confirmed in the enlarged group of NFPAs. Difference in the methylation profiles between invasive and non-invasive NFPAs is very slight. Nevertheless, invasiveness-related aberrant epigenetic deregulation of the particular genes was found including upregulation of ITPKB and downregulation CNKSR1 in invasive tumors.

摘要

无功能垂体腺瘤（NFPAs）是最常见的颅内肿瘤之一，但它们的分子背景，包括表观遗传调控的变化，仍知之甚少。我们对 34 例 NFPAs 和正常垂体样本进行了全基因组 DNA 甲基化谱分析。在一组 75 例患者中，评估了所选基因组区域的甲基化状态和相应基因的表达水平。与正常垂体相比，NFPAs 表现出明显的全局甲基化谱。初步功能分析表明，异常的 DNA 甲基化可能导致与癌症相关的途径失调。在扩大的 NFPAs 组中，SFN、STAT5A、DUSP1、PTPRE 和 FGFR2 的启动子过度甲基化和表达水平降低得到了证实。侵袭性和非侵袭性 NFPAs 之间的甲基化谱差异非常小。然而，在侵袭性肿瘤中发现了与侵袭性相关的特定基因的异常表观遗传失调，包括 ITPKB 的上调和 CNKSR1 的下调。