Jarmalaite Sonata, Laurinaviciene Aida, Tverkuviene Justina, Kalinauskaite Neringa, Petroska Donatas, Böhling Tom, Husgafvel-Pursiainen Kirsti
Vilnius University, Lithuania.
Cancer Genet. 2011 Jul;204(7):398-404. doi: 10.1016/j.cancergen.2011.07.002.
ZAC/PLAGL1 is a novel imprinted tumor suppressor gene encoding an important inducer of cell cycle arrest and apoptosis, and found to be lost during tumorigenesis. We analyzed the significance of ZAC in the development of a rare, usually benign tumor of the adrenal gland: pheochromocytoma (PCC). Twenty-four PCCs were analyzed for the loss of the active nonimprinted allele of ZAC, and nine of the twenty-four PCCs were also assayed for expression of the protein. In thirteen of the cases, a paired nonmalignant tissue was available for analysis. Methylation-specific polymerase chain reaction revealed frequent (15 of 23, 65%) loss of unmethylated DNA in the imprinting control region of ZAC. Immunohistochemistry identified reduced ZAC expression in 56% (5 of 9) of the subset cases. Four of the five PCC cases where reduced expression of ZAC was observed were also positive for the loss of the active ZAC allele. Additionally, the loss of ZAC expression was also found to be frequent in a series of capillary hemangioblastomas and gliomas (6 of 6, 100%, and 17 of 27, 63%, respectively) examined for comparison. In conclusion, our study suggests the involvement of the imprinted ZAC gene in the pathogenesis of PCC.
ZAC/PLAGL1是一种新的印记肿瘤抑制基因，编码细胞周期停滞和凋亡的重要诱导因子，且发现在肿瘤发生过程中缺失。我们分析了ZAC在一种罕见的、通常为良性的肾上腺肿瘤：嗜铬细胞瘤（PCC）发生发展中的意义。对24例PCC进行了ZAC活性非印记等位基因缺失分析，其中9例还检测了该蛋白的表达。在13例病例中，有配对的非恶性组织可供分析。甲基化特异性聚合酶链反应显示，ZAC印记控制区域未甲基化DNA频繁缺失（23例中的15例，65%）。免疫组织化学鉴定出在56%（9例中的5例）的亚组病例中ZAC表达降低。在观察到ZAC表达降低的5例PCC病例中，有4例活性ZAC等位基因缺失也呈阳性。此外，在一系列用于比较的毛细血管性成血管细胞瘤和胶质瘤中（分别为6例中的6例，100%，以及27例中的17例，63%）也发现ZAC表达缺失很常见。总之，我们的研究提示印记ZAC基因参与了PCC的发病机制。
