Frequent copresence of methylated DNA and fragmented nucleosomal DNA in plasma of lymphoma patients

Frequent copresence of methylated DNA and fragmented nucleosomal DNA in plasma of lymphoma patients
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DOI:
10.1016/s0009-8981(03)00279-1
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发表时间:
2003-09-01
影响因子:
5
通讯作者:
Dalay, N
Dalay, N
中科院分区:
医学3区
文献类型:
--
作者:
Deligezer, U;Yaman, F;Dalay, N

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背景:癌症患者血浆/血清中的循环DNA已被证明反映了肿瘤DNA的特征,包括甲基化、点突变和微卫星不稳定性等分子变化。肿瘤细胞的凋亡性死亡所致的血浆中核小体DNA片段化也可能是肿瘤DNA的一个指征。在这项研究中,我们比较分析了淋巴增殖性疾病患者血浆DNA甲基化和核小体DNA碎片的存在。方法:采用甲基化敏感的限制性内切酶相关聚合酶链式反应检测抑癌基因p16第一外显子甲基化情况。用凝胶电泳法分析血浆DNA片段化程度。结果:p16基因甲基化发生率为73%,而20例健康对照组均为阴性。81%的患者可检测到核小体DNA片段化。在67%的患者中,观察到这两个参数的共同存在。这两个参数的出现是一种常见事件,可作为早期诊断和疾病随访的标志。(C)2003爱思唯尔B.V.保留所有权利。
Background: The circulating DNA in plasma/serum of cancer patients has been shown to reflect the characteristics of the tumor DNA including molecular changes, such as rnethylation, point mutations and microsatellite instability. Fragmented nucleosomal DNA in plasma resulting from apoptotic death of the tumor cells may also provide an indication for tumor DNA. In this study, we comparatively analysed plasma DNA methylation and presence of fragmented nucleosomal DNA in patients with lymphoproliferative diseases. Methods: Methylation in the first exon of the tumor supressor gene p16 was investigated by the methylation-sensitive restriction enzyme-related PCR. DNA fragmentation in plasma was analysed by gel electrophoresis. Results: p16 gene methylation was found to occur in 73% of patients but in none of the 20 healthy controls. Nucleosomal DNA fragmentation was detectable in 81% of patients. In 67% of patients, copresence of both parameters was observed. Presence of both parameters a frequent event and may be used as a marker for early diagnosis and during the follow-up of the disease. (C) 2003 Elsevier B.V. All rights reserved.