Verdelli Chiara, Forno Irene, Vaira Valentina, Corbetta Sabrina
Laboratory of Molecular Biology, IRCCS Policlinico San Donato, San Donato Milanese, MI, Italy.
Endocrine. 2015 Jun;49(2):324-32. doi: 10.1007/s12020-015-0555-4. Epub 2015 Feb 27.
Epigenetics alterations are involved in tumorigenesis and have been identified in endocrine neoplasia. In particular, DNA methylation, microRNAs deregulations and histone methylation impairment are detected in tumors of the parathyroid glands. Parathyroid tumors are the second most common endocrine neoplasia following thyroid cancer in women, and it is associated with primary hyperparathyroidism, a disease sustained by PTH hypersecretion. Despite the hallmark of global promoter hypomethylations was not detectable in parathyroid tumors, increase of hypermethylation in specific CpG islands was detected in the progression from benign to malignant parathyroid tumors. Furthermore, deregulation of a panel of embryonic-related microRNAs (miRNAs) was documented in parathyroid tumors compared with normal glands. Impaired expression of the histone methyltransferases EZH2, BMI1, and RIZ1 have been described in parathyroid tumors. Moreover, histone methyltransferases have been shown to be modulated by the oncosuppressors HIC1, MEN1, and HRPT2/CDC73 gene products that characterize tumorigenesis of parathyroid adenomas and carcinomas, respectively. The epigenetic scenario in parathyroid tumors have just began to be decoded but emerging data highlight the involvement of an embryonic gene signature in parathyroid tumor development.
表观遗传学改变参与肿瘤发生，并且已在内分泌肿瘤中得到确认。特别是，在甲状旁腺肿瘤中检测到DNA甲基化、微小RNA失调和组蛋白甲基化损伤。甲状旁腺肿瘤是女性继甲状腺癌之后第二常见的内分泌肿瘤，它与原发性甲状旁腺功能亢进有关，原发性甲状旁腺功能亢进是一种由甲状旁腺激素分泌过多引起的疾病。尽管在甲状旁腺肿瘤中未检测到整体启动子低甲基化的特征，但在从良性到恶性甲状旁腺肿瘤的进展过程中，检测到特定CpG岛的高甲基化增加。此外，与正常腺体相比，甲状旁腺肿瘤中一组与胚胎相关的微小RNA（miRNA）失调。在甲状旁腺肿瘤中已描述了组蛋白甲基转移酶EZH2、BMI1和RIZ1的表达受损。此外，组蛋白甲基转移酶已被证明分别受抑癌基因HIC1、MEN1和HRPT2/CDC73基因产物的调节，这些基因产物分别是甲状旁腺腺瘤和癌肿瘤发生的特征。甲状旁腺肿瘤中的表观遗传学情况刚刚开始被解读，但新出现的数据突出了胚胎基因特征在甲状旁腺肿瘤发展中的作用。
