Detection of p16 hypermethylation in circulating plasma DNA of non-small cell lung cancer patients

Detection of p16 hypermethylation in circulating plasma DNA of non-small cell lung cancer patients
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DOI:
10.1016/s0304-3835(02)00496-2
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发表时间:
2002-12-15
期刊:
影响因子:
9.7
通讯作者:
Cheng, SJ
Cheng, SJ
中科院分区:
医学1区
文献类型:
--
作者:
An, Q;Liu, Y;Cheng, SJ

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我们使用改进的半巢式甲基化特异性PCR (MSP)检测了105例非小细胞肺癌(NSCLC)患者(65例鳞状细胞癌(SCC)和40例腺癌(ADC))和92例匹配肿瘤DNA样本的血浆DNA中p16基因的肿瘤相关异常高甲基化。该技术增加了从不同阶段的DNA样品中检测p16超甲基化的敏感性。73.3%(77/105)的血浆样本和79.3%(73/92)的肿瘤样本存在P16高甲基化。在肿瘤样本中p16序列甲基化的病例中,87.7%(64/73)的患者在相应的血浆DNA中也表现出这种表观遗传改变。只有肿瘤细胞p16基因高度甲基化的患者在其血浆样本中表现出异常甲基化。在SCC和ADC的不同临床分期中,血浆DNA中p16高甲基化的频率与相应肿瘤中p16高甲基化的频率几乎相同,但I期ADC除外。我们的研究表明p16的异常甲基化可能是NSCLC患者早期诊断和随访的一个很好的生物标志物,而MSP是实现这些目的的可靠方法。(C) 2002爱思唯尔科学爱尔兰有限公司版权所有。
We detected tumor-associated aberrant hypermethylation of the p16 gene in plasma DNA from 105 non-small cell lung cancer (NSCLC) patients (65 squamous cell carcinoma (SCC) and 40 adenocarcinoma (ADC)) and 92 matched tumor DNA samples, using a modified semi-nested methylation-specific PCR (MSP). This technique increased the sensibility of detecting p16 hypermethylation from DNA samples in varying stages. p16 hypermethylation was present in 73.3% (77/105) of the plasma samples, and 79.3% (73/92) of the tumor samples. Among those cases with methylated p16 sequence in tumor samples, 87.7% (64/73) also demonstrated this epigenetic alteration in the corresponding plasma DNA. Only patients whose tumor cells had hypermethylated p16 gene exhibited aberrant methylation in their plasma samples. Regarding different clinical stages of SCC and ADC, the frequencies of p16 hypermethylation in plasma DNA were nearly the same as those in corresponding tumors, except for stage I ADC. Our study indicated that aberrant methylation of p16 may be an excellent biomarker for early diagnosis and follow-up of NSCLC patients, and MSP is a reliable method for these purposes. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.