Promoter methylation and silencing of PTEN in gastric carcinoma
Promoter methylation and silencing of PTEN in gastric carcinoma
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DOI：
10.1038/labinvest.3780422
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发表时间：
2002-03-01
影响因子：
5
通讯作者：
Kim, WH
中科院分区：
文献类型：
--
作者：
Kang, YH;Lee, HS;Kim, WH
PTEN/MMAC1/TEP1基因(在多种晚期癌症中缺失10号染色体上的磷酸酶和张力蛋白同源基因/突变/转化生长因子-β调控的上皮细胞富集型磷酸酶1)调节Akt的信号通路，是一个新的肿瘤抑制基因，与多种癌症有关。由于许多肿瘤抑制基因被异常的启动子甲基化所沉默，我们用甲基化特异性的聚合酶链式反应检测了PTEN的5‘CpG岛的甲基化状态。应用组织芯片免疫组织化学方法检测310例胃癌组织中PTEN蛋白的表达变化，并对其相关的临床病理特征进行分析。连续310例胃癌中，62例(20%)PTEN表达缺失。PTEN表达改变与肿瘤深度和大小、淋巴侵犯、晚期、pTNM分期和患者生存期显著相关(p<；0.001)。在66例胃癌组织中，26例(39%)存在PTEN基因启动子甲基化，其中19例(73%)PTEN基因启动子甲基化缺失。PTEN基因表达异常与启动子甲基化显著相关(p<；0.001)。总之，PTEN基因沉默在胃癌中频繁发生，启动子异常甲基化是PTEN基因沉默的主要机制。PTEN基因的异常与肿瘤的进展、转移和生存有关。
The PTEN/MMAC1/TEP1 gene (phosphatase and tensin homolog deleted on chromosome 10/mutated in multiple advanced cancers/TGF-beta regulated and epithelial cell enriched phosphatase 1), which regulates the signaling pathways of Akt, is a novel tumor suppressor gene implicated in multiple cancers. Because a number of tumor suppressor genes are known to be silenced by aberrant promoter methylation, we examined the methylation status of the 5' CpG islands of PTEN using methylation-specific PCR. The altered expression of PTEN in 310 gastric carcinomas was analyzed by immunohistochemical staining using tissue-array and clinicopathologic profiles related to PTEN expression were characterized. Of 310 consecutive gastric carcinomas, 62 cases (20%) showed expression loss of PTEN. Altered PTEN expression was significantly associated with tumor depth and size, lymphatic invasion, advanced stage, pTNM stage, and patient survival (p < 0.001). The promoter methylation frequency of PTEN was found to be present in 26 (39%) of 66 cases examined, and 19 (73%) of 26 gastric cancer tissues showing promoter methylation exhibited the loss of PTEN expression. Abnormalities in the expression of PTEN significantly correlated with promoter methylation (p < 0.001). In conclusion, silencing of the PTEN gene occurs frequently in gastric carcinoma and aberrant promoter methylation is a major mechanism of silencing of the PTEN gene. The abnormalities of the PTEN gene are associated with tumor progression, metastasis, and survival.