散发性垂体腺瘤中肿瘤抑制基因的遗传和表观遗传突变。
Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma.
机构信息
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States.
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, United States.
出版信息
Mol Cell Endocrinol. 2014 Apr 5;386(1-2):16-33. doi: 10.1016/j.mce.2013.09.006. Epub 2013 Sep 11.
Human pituitary adenomas are the most common intracranial neoplasms. Approximately 5% of them are familial adenomas. Patients with familial tumors carry germline mutations in predisposition genes, including AIP, MEN1 and PRKAR1A. These mutations are extremely rare in sporadic pituitary adenomas, which therefore are caused by different mechanisms. Multiple tumor suppressive genes linked to sporadic tumors have been identified. Their inactivation is caused by epigenetic mechanisms, mainly promoter hypermethylation, and can be placed into two groups based on their functional interaction with tumor suppressors RB or p53. The RB group includes CDKN2A, CDKN2B, CDKN2C, RB1, BMP4, CDH1, CDH13, GADD45B and GADD45G; AIP and MEN1 genes also belong to this group. The p53 group includes MEG3, MGMT, PLAGL1, RASSF1, RASSF3 and SOCS1. We propose that the tumor suppression function of these genes is mainly mediated by the RB and p53 pathways. We also discuss possible tumor suppression mechanisms for individual genes.
人类垂体腺瘤是最常见的颅内肿瘤。其中约 5%为家族性腺瘤。携带易感基因（包括 AIP、MEN1 和 PRKAR1A）种系突变的患者存在家族性肿瘤。这些突变在散发的垂体腺瘤中极为罕见，因此由不同的机制引起。已经鉴定出与散发肿瘤相关的多个肿瘤抑制基因。它们的失活是由表观遗传机制引起的，主要是启动子超甲基化，并可以根据它们与肿瘤抑制因子 RB 或 p53 的功能相互作用分为两组。RB 组包括 CDKN2A、CDKN2B、CDKN2C、RB1、BMP4、CDH1、CDH13、GADD45B 和 GADD45G；AIP 和 MEN1 基因也属于这一组。p53 组包括 MEG3、MGMT、PLAGL1、RASSF1、RASSF3 和 SOCS1。我们提出这些基因的肿瘤抑制功能主要是通过 RB 和 p53 途径介导的。我们还讨论了个别基因的可能肿瘤抑制机制。
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