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甲状旁腺肿瘤中的 DNA 甲基化改变。

Alterations of DNA methylation in parathyroid tumors.

机构信息

Genetic Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.

Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.

出版信息

Mol Cell Endocrinol. 2018 Jul 5;469:60-69. doi: 10.1016/j.mce.2017.05.010. Epub 2017 May 10.

Abstract

Parathyroid tumors are common endocrine neoplasias associated with primary hyperparathyroidism, a metabolic disorder characterized by parathormone hypersecretion. Parathyroid neoplasia are frequently benign adenomas or multiple glands hyperplasia, while malignancies are rare. The epigenetic scenario in parathyroid tumors has just begun to be decoded: DNA methylation, histones and chromatin modifiers expression have been investigated so far. The main findings suggest that DNA methylation and chromatin remodeling are active and deregulated in parathyroid tumors, cooperating with genetic alterations to drive the tumor phenotype: the tumor suppressors menin and parafibromin, involved in parathyroid tumorigenesis, interact with chromatin modifiers, defining distinct epigenetic derangements. Many epigenetic alterations identified in parathyroid tumors are common to those in human cancers; moreover, some aspects of the epigenetic profile resemble epigenetic features of embryonic stem cells. Epigenetic profile may contribute to define the heterogeneity of parathyroid tumors and to provide targets for new therapeutic approaches.

摘要

甲状旁腺肿瘤是常见的内分泌肿瘤,与甲状旁腺功能亢进症有关,这是一种以甲状旁腺激素分泌过多为特征的代谢紊乱。甲状旁腺肿瘤通常为良性腺瘤或多腺体增生,而恶性肿瘤则较为罕见。甲状旁腺肿瘤的表观遗传学情况才刚刚开始被揭示:迄今为止,已经研究了 DNA 甲基化、组蛋白和染色质修饰剂的表达。主要发现表明,DNA 甲基化和染色质重塑在甲状旁腺肿瘤中是活跃且失调的,与遗传改变合作驱动肿瘤表型:参与甲状旁腺肿瘤发生的肿瘤抑制因子 menin 和 parafibromin 与染色质修饰剂相互作用,定义了不同的表观遗传失调。在甲状旁腺肿瘤中鉴定出的许多表观遗传改变与人类癌症中的改变是共同的;此外,表观遗传谱的某些方面类似于胚胎干细胞的表观遗传特征。表观遗传谱可能有助于定义甲状旁腺肿瘤的异质性,并为新的治疗方法提供靶点。

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