Methylation of promoter region in p27 gene plays a role in the development of lymphoid malignancies.
Methylation of promoter region in p27 gene plays a role in the development of lymphoid malignancies.
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p27基因启动子区域的甲基化在淋巴恶性肿瘤的发生中发挥作用。
DOI：
10.3892/ijo.22.3.561
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发表时间：
2003
影响因子：
5.2
通讯作者：
K. Aozasa
中科院分区：
文献类型：
--
作者：
S. Nakatsuka;Angen Liu;Masayuki Yao;T. Takakuwa;Y. Tomita;Y. Hoshida;Mieko Nishiu;K. Aozasa
P27属于周期蛋白依赖性激酶抑制剂家族，在调节细胞周期进程中起重要作用。这些基因的表达受到启动子区域甲基化的表观遗传抑制。在本研究中，我们检测了70例非霍奇金淋巴瘤中p27启动子区蛋白表达和甲基化状态，并通过Ki-67指数揭示了它们与肿瘤细胞增殖活性的关系。b细胞淋巴瘤35例，t细胞淋巴瘤11例，NK/ t细胞淋巴瘤23例，类型不详1例。免疫组化结果显示，35例患者中有24例（69%）p27蛋白表达缺失。p27蛋白表达与Ki-67指数呈显著负相关。单链构象多态性（SSCP）测序未检出点突变。亚硫酸氢盐测序分析显示，68例患者中有17例（25%）出现p27启动子区甲基化，p27基因起始密码子周围的几个特定CpG位点被优先甲基化。22例p27蛋白表达缺失患者中，8例p27基因5′区CpG岛发生甲基化。这些发现表明，基因甲基化在p27表达缺失中起作用，p27表达缺失使细胞具有增殖优势。
p27 belong to the cyclin-dependent kinase inhibitor family and plays an important role in regulation of cell cycle progression. Expression of these genes is epigenetically suppressed by methylation of their promoter regions. In this study, we examined protein expression and methylation status of the promoter region of p27 in 70 cases with non-Hodgkin's lymphoma and their relationship with proliferative activity of the tumor cells as revealed by Ki-67 index. There were 35 cases of B-cell, 11 of T-cell, 23 of NK/T-cell lymphoma, and 1 undetermined type. Immunohistochemically the loss of p27 protein expression was observed in 24 (69%) of 35 cases. Significant inverse correlation between p27 protein expression and Ki-67 index was found. Single strand conformation polymorphism (SSCP) followed by sequencing could not detect point mutations in any of the 68 cases. Bisulfite sequencing analysis showed that methylation of the promoter region of p27 were observed in 17 (25%) of 68 cases, in that several specific CpG sites around the start codon of p27 gene were preferentially methylated. Eight of 22 cases with loss of p27 protein expression showed methylation in CpG island of 5' region of p27 gene. These findings suggested that gene methylation plays a role in loss of expression of p27, which gives the cells proliferative advantages.