Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling
Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling
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DOI：
10.1111/j.1755-148x.2008.00484.x
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发表时间：
2008-10-01
影响因子：
4.3
通讯作者：
Riker, Adam I.
中科院分区：
文献类型：
--
作者：
Liu, Suhu;Ren, Suping;Riker, Adam I.
通过启动子CpG岛的异常甲基化使肿瘤相关基因失活，被认为有助于肿瘤的发生和发展。因此，我们通过筛选30个感兴趣的基因以寻找启动子超甲基化的证据，检查了20个黑色素瘤细胞株和40个新鲜获得的黑色素瘤样本，研究了皮肤黑色素瘤涉及的启动子甲基化事件。利用定量甲基化特异性聚合酶链式反应，我们在黑色素瘤细胞系和新鲜获取的组织样本中发现了5个基因(SOCS1、SOCS2、RAR-β2、TNFSF10C和TNFSF10D)，其高甲基化频率从50%到80%不等。18个基因(LOX、RASSF1A、WFDC1、TM、APC、TFPI2、TNFSF10A、CDKN2A、MGMT、TIMP3、ASC、TPM1、IRF8、CIITA-PIV、CDH1、SYK、HOXB13和DAPK1)的甲基化频率较低(2-30%)。两个基因(CDKN1B和PTEN)和其他五个基因(RECK、IRF7、PAWR、TNFSF10B和RB)在这里筛选的样本中没有甲基化，这两个基因在黑色素瘤中被报道为甲基化。与原始样本相比，子代黑色素瘤细胞株显示出相同的甲基化模式，同一患者的同步转移病变也是如此。我们鉴定了四个基因(TNFSF10C、TNFSF10D、LOX和TPM1)，它们在黑色素瘤中从未被鉴定为高甲基化，总的甲基化频率分别为60%、80%、50%和10%，假设这些基因可能在黑色素瘤的进展中发挥重要作用。
The inactivation of tumor-related genes through the aberrant methylation of promoter CpG islands is thought to contribute to tumor initiation and progression. We therefore investigated promoter methylation events involved in cutaneous melanoma by screening 30 genes of interest for evidence of promoter hypermethylation, examining 20 melanoma cell lines and 40 freshly procured melanoma samples. Utilizing quantitative methylation-specific PCR, we identified five genes (SOCS1, SOCS2, RAR-beta 2, TNFSF10C, and TNFSF10D) with hypermethylation frequencies ranging from 50% to 80% in melanoma cell lines as well as freshly procured tissue samples. Eighteen genes (LOX, RASSF1A, WFDC1, TM, APC, TFPI2, TNFSF10A, CDKN2A, MGMT, TIMP3, ASC, TPM1, IRF8, CIITA-PIV, CDH1, SYK, HOXB13, and DAPK1) were methylated at lower frequencies (2-30%). Two genes (CDKN1B and PTEN), previously reported as methylated in melanoma, and five other genes (RECK, IRF7, PAWR, TNFSF10B, and Rb) were not methylated in the samples screened here. Daughter melanoma cell lines showed identical methylation patterns when compared with original samples from which they were derived, as did synchronous metastatic lesions from the same patient. We identified four genes (TNFSF10C, TNFSF10D, LOX, and TPM1) that have never before been identified as hypermethylated in melanoma, with an overall methylation frequency of 60, 80, 50, and 10%, respectively, hypothesizing that these genes may play an important role in melanoma progression.