Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin S B, Herman J G
Tumor Biology, The Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Cancer Res. 1999 Jan 1;59(1):67-70.
Recent evidence suggests that tumor cells may release DNA into the circulation, which is enriched in the serum and plasma, allowing detection of ras and p53 mutations and microsatellite alterations in the serum DNA of cancer patients. We examined whether aberrant DNA methylation might also be found in the serum of patients with non-small cell lung cancer. We tested 22 patients with non-small cell lung cancer using methylation-specific PCR, searching for promoter hypermethylation of the tumor suppressor gene p16, the putative metastasis suppressor gene death-associated protein kinase, the detoxification gene glutathione S-transferase P1, and the DNA repair gene O6-methylguanine-DNA-methyltransferase. Aberrant methylation of at least one of these genes was detected in 15 of 22 (68%) NSCLC tumors but not in any paired normal lung tissue. In these primary tumors with methylation, 11 of 15 (73%) samples also had abnormal methylated DNA in the matched serum samples. Moreover, none of the sera from patients with tumors not demonstrating methylation was positive. Abnormal promoter methylation in serum DNA was found in all tumor stages. Although these results need to be confirmed in larger studies and in other tumor types, detection of aberrant promoter hypermethylation of cancer-related genes in serum may be useful for cancer diagnosis or the detection of recurrence.
最近的证据表明，肿瘤细胞可能会将DNA释放到循环系统中，这些DNA在血清和血浆中富集，从而能够检测癌症患者血清DNA中的ras和p53突变以及微卫星改变。我们研究了非小细胞肺癌患者的血清中是否也能发现异常的DNA甲基化。我们使用甲基化特异性PCR对22例非小细胞肺癌患者进行检测，寻找肿瘤抑制基因p16、假定的转移抑制基因死亡相关蛋白激酶、解毒基因谷胱甘肽S-转移酶P1以及DNA修复基因O6-甲基鸟嘌呤-DNA甲基转移酶的启动子高甲基化。在22例非小细胞肺癌肿瘤中有15例（68%）检测到这些基因中至少有一个存在异常甲基化，但在任何配对的正常肺组织中均未检测到。在这些发生甲基化的原发性肿瘤中，15例样本中有11例（73%）在配对的血清样本中也存在异常甲基化的DNA。此外，肿瘤未显示甲基化的患者的血清均为阴性。血清DNA中的异常启动子甲基化在所有肿瘤分期中均有发现。尽管这些结果需要在更大规模的研究和其他肿瘤类型中得到证实，但检测血清中癌症相关基因的异常启动子高甲基化可能有助于癌症诊断或复发检测。
