Martinez-Glez V, Franco-Hernandez C, Gonzalez-Gomez P, Isla A, De Campos J M, Vaquero J, Gutierrez M, Casartelli C, Rey J A
Unidad de Investigación, Hospital Universitario La Paz, Madrid, Spain.
Neoplasma. 2007;54(2):123-6.
The DAPK1 gene works as a regulator of apoptosis and is frequently inactivated in cancer by aberrant promoter hypermethylation. Loss of DAPK1 expression is associated with a selective advantage for tumor cells to resist apoptotic stimuli, allowing them to separate from the original tumor; from this point of view, DAPK1 could be considered a tumor metastases inhibitor gene. To verify the participation of DAPK1 silencing in cerebral invasion, we analyzed its promoter methylation status in a series of 28 samples from cerebral metastases using MSP and sequencing of the MSP-product. We have found hypermethylation in 53.6% (15/28) metastatic tumor samples as well as in 27.8% (5/18) of its peripheral blood samples. Our data suggest an important role of DAPK1 for silencing through promoter CpG island hypermethylation in the development of brain metastases from solid tumors. The detection of aberrant hypermethylation on DAPK1 promoter from peripheral blood samples has potential clinical implications as a tumor prognosis marker.
DAPK1基因作为细胞凋亡的调节因子，在癌症中常因异常的启动子高甲基化而失活。DAPK1表达缺失与肿瘤细胞抵抗凋亡刺激的选择性优势相关，使它们能够从原发肿瘤中分离出来；从这个角度来看，DAPK1可被视为一种肿瘤转移抑制基因。为了验证DAPK1沉默在脑侵袭中的作用，我们使用甲基化特异性PCR（MSP）和MSP产物测序分析了28例脑转移瘤样本系列中其启动子甲基化状态。我们发现53.6%（15/28）的转移瘤样本以及27.8%（5/18）的外周血样本中存在高甲基化。我们的数据表明，DAPK1通过启动子CpG岛高甲基化沉默在实体瘤脑转移发生发展中起重要作用。从外周血样本中检测DAPK1启动子异常高甲基化作为肿瘤预后标志物具有潜在临床意义。
