Noninvasive detection of tumor-associated mutations from circulating cell-free DNA in hepatocellular carcinoma patients by targeted deep sequencing.
Noninvasive detection of tumor-associated mutations from circulating cell-free DNA in hepatocellular carcinoma patients by targeted deep sequencing.
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DOI：
10.18632/oncotarget.9629
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发表时间：
2016-06-28
期刊：
影响因子：
--
通讯作者：
Mao Y
中科院分区：
文献类型：
--
作者：
Liao W;Yang H;Xu H;Wang Y;Ge P;Ren J;Xu W;Lu X;Sang X;Zhong S;Zhang H;Mao Y
循环游离DNA（cfDNA）的检测对于评估患有肝细胞癌（HCC）的患者中的肿瘤生物学具有潜在的临床价值，然而许多传统测定缺乏稳健性。该研究首次应用高通量测序平台从循环肿瘤衍生DNA（ctDNA）中检测HCC中的肿瘤相关突变，并评估该方法的实用性和可行性。使用MiSeq™系统，分析血浆和匹配的肿瘤DNA样品中的TERT、CTNNB1和TP53基因中的热点突变，这些突变已被证实为HCC中最普遍的突变。我们比较了肿瘤和血浆数据，并前瞻性地研究了ctDNA中检测到的显著突变与患者临床结局之间的关系。在41例患者中，我们在8例（19.5%）血浆样本中检测到HCC的肿瘤相关突变。其中，一个在ctDNA中显示出肿瘤相关突变，但在我们用来检测的肿瘤组织中没有。我们还发现，在血管侵犯患者中，ctDNA突变更容易检测到（P=0.041），预测无复发生存时间更短（P<0.001）。可检测的突变与cfDNA浓度之间没有关系（P=0.818）。我们的研究结果表明，在血浆中检测到的肿瘤相关突变与血管浸润有关，并可能用于预测HCC患者的无复发生存时间较短。这种生物标志物可以克服肿瘤异质性的局限性。此外，如果不同基因中的多个突变被组合，则诊断性能得到改善。
Detection of circulating cell-free DNA (cfDNA) has potential clinical value for assessing tumor biology in patients with hepatocellular carcinoma (HCC), yet many traditional assays lack robustness. This study was the first to apply a high-throughput sequencing platform to detect tumor-associated mutations in HCC from circulating tumor-derived DNA (ctDNA) and to evaluate the utility and feasibility of this approach. Using the MiSeq™ system, plasma and matched tumor DNA samples were analyzed for hotspot mutations in the TERT, CTNNB1, and TP53 genes that had been verified as the most prevalent mutations in HCC. We compared tumor and plasma data and prospectively investigated the association between significant mutations detected in ctDNA and the patients' clinical outcomes. In 41 patients, we detected tumor-associated mutations for HCC in 8 (19.5%) plasma samples. Among them, one showed a tumor-associated mutation in ctDNA but not in the tumor tissue which we used to detect. We also found that ctDNA with mutations could be detected more easily in patients who suffered vascular invasion (P=0.041) and predicted a shorter recurrence-free survival time (P<0.001). There was no relationship between detectable mutations and concentration of cfDNA (P=0.818). The results of our study suggest that tumor-associated mutations detected in plasma are associated with vascular invasion and might be used to predict a shorter recurrence-free survival time for HCC patients. This kind of biomarker can overcome the limitations of tumor heterogeneity. Moreover, the diagnostic performance is improved if multiple mutations in different genes are combined.
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影响因子：
2.9
作者：
Mittal S;El-Serag HB
通讯作者：
El-Serag HB
影响因子：
16.6
作者：
Sausen M;Phallen J;Adleff V;Jones S;Leary RJ;Barrett MT;Anagnostou V;Parpart-Li S;Murphy D;Kay Li Q;Hruban CA;Scharpf R;White JR;O'Dwyer PJ;Allen PJ;Eshleman JR;Thompson CB;Klimstra DS;Linehan DC;Maitra A;Hruban RH;Diaz LA Jr;Von Hoff DD;Johansen JS;Drebin JA;Velculescu VE
通讯作者：
Velculescu VE
影响因子：
15.9
作者：
Gul, Nuray;Babes, Liane;van Egmond, Marjolein
通讯作者：
van Egmond, Marjolein
DOI：
10.1073/pnas.0507904102
发表时间：
2005-11-08
影响因子：
11.1
作者：
Diehl, F;Li, M;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
13.5
作者：
Kojiro, Masamichi;Wanless, Ian R.;Toniakos, Dina
通讯作者：
Toniakos, Dina