Plasma DNA microsatellite panel as sensitive and tumor-specific marker in lung cancer patients
Plasma DNA microsatellite panel as sensitive and tumor-specific marker in lung cancer patients
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DOI：
10.1002/ijc.11079
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发表时间：
2003-06-20
影响因子：
6.4
通讯作者：
Oudet, P
中科院分区：
文献类型：
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作者：
Beau-Faller, M;Gaub, MP;Oudet, P
大多数肺癌患者的循环血浆 DNA 中存在肿瘤衍生的遗传改变，可以将其用作诊断工具。我们使用荧光微卫星分析来检测 34 名因肺癌接受支气管镜检查的患者的血浆和肿瘤 DNA 的变化，其中包括 11 名小细胞肺癌 (SCLC) 和 23 名非小细胞肺癌 (NSCLC)（12 名腺癌，11 名鳞状细胞癌）和 20 名对照。使用来自 9 个染色体区域 3p21、3p24、5q、9p、9q、13q、17p、17q 和 20q 的选定 12 个微卫星组进行等位基因分型。 88% 的患者（34 名患者中的 30 名）发现血浆 DNA 等位基因失衡 (AI)，在 SCLC 和 NSCLC 中具有相似的敏感性。在 24 个配对的可用肿瘤组织中，83%（24 个中的 20 个）呈现至少 1 个 AI。在这些患者中，85%（20 人中的 17 人）在配对血浆 DNA 中也呈现出至少 1 个 AI，但配对血浆和肿瘤 DNA 中等位基因改变的位置可能不同，表明存在异质肿瘤克隆。 20 名对照者均未显示血浆或支气管 DNA 改变。由六个标记（位于 3p、5q、9p、9q）组成的精简组显示出 85% 的灵敏度。此外，可以专门使用 SCLC 中 3p 和 17p 13 以及 NSCLC 患者中 5q、9p、9q 和 20q 处的不同微卫星组。使用该靶向组对血浆 DNA 进行分析可能是一种有价值的非侵入性测试，也是在不评估肿瘤的情况下监测疾病进展的有用工具。 (C) 2003 Wiley-Liss, Inc.
The majority of lung cancer patients have tumor-derived genetic alterations in circulating plasma DNA that could be exploited as a diagnostic tool. We used fluorescent microsatellite analysis to detect alterations in plasma and tumor DNA in 34 patients who underwent bronchoscopy for lung cancer, including 11 small cell lung cancer (SCLC) and 23 nonsmall cell lung cancer (NSCLC) (12 adenocarcinomas, 11 squamous cell carcinomas) and 20 controls. Allelotyping was performed with a selected panel of 12 microsatellites from 9 chromosomal regions 3p21, 3p24, 5q, 9p, 9q, 13q, 17p, 17q and 20q. Plasma DNA allelic imbalance (AI) was found in 88% (30 of 34 patients), with a similar sensitivity in SCLC and NSCLC. In the 24 paired available tumor tissues, 83% (20 of 24) presented at least 1 AI. Among these patients, 85% (17 of 20) presented also at least 1 AI in paired plasma DNA, but the location of the allelic alterations in paired plasma and tumor DNA could differ, suggesting the presence of heterogeneous tumor clones. None of the 20 controls displayed plasma or bronchial DNA alteration. A reduced panel of six markers (at 3p, 5q, 9p, 9q) showed a sensitivity of 85%. Moreover, a different panel of microsatellites at 3p and 17p 13 in SCLC and at 5q, 9p, 9q and 20q in NSCLC patients could be specifically used. Analysis of plasma DNA using this targeted panel could be a valuable noninvasive test and a useful tool to monitor disease progression without assessing the tumor. (C) 2003 Wiley-Liss, Inc.