Detection of ctDNA with Personalized Molecular Barcode NGS and Its Clinical Significance in Patients with Early Breast Cancer
Detection of ctDNA with Personalized Molecular Barcode NGS and Its Clinical Significance in Patients with Early Breast Cancer
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DOI：
10.1016/j.tranon.2020.100787
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发表时间：
2020-08-01
影响因子：
5
通讯作者：
Noguchi, Shinzaburo
中科院分区：
文献类型：
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作者：
Yoshinami, Tetsuhiro;Kagara, Naofumi;Noguchi, Shinzaburo
我们尝试利用分子条形码新一代测序 (MB-NGS) 来检测循环肿瘤 DNA (ctDNA)，与基于 PCR 的方法相比，分子条形码新一代测序 (MB-NGS) 可以更轻松地进行定制，以高灵敏度检测各种突变。对由 I 期或 II 期患者乳腺肿瘤中 13 个最常见突变基因组成的基因组进行测序，发现 62% (62/100) 的肿瘤中 12 个基因中有 95 个体细胞突变。然后，通过针对每种体细胞突变定制的 MB-NGS 分析每位患者 (n = 62) 术前的血浆 DNA，结果在 16.1% (10/62) 的患者中检测到 ctDNA。 ctDNA 与生物侵袭性表型显着相关，包括肿瘤体积大 (P = .004)、淋巴结阳性 (P = .009)、高组织学分级 (P < .001)、ER 阴性 (P = .018)、PR 阴性 (P = .017) 和 HER2 阳性 (P = .046)。此外，有 ctDNA 的患者 (n = 10) 的远期无病生存率明显低于没有 ctDNA 的患者 (n = 52) (P < .001)。我们的结果表明，针对每个突变进行个性化的 MB-NGS 可以在诊断时以高灵敏度检测早期乳腺癌患者的 ctDNA，并且它似乎有潜力作为临床上有用的肿瘤标志物来预测其预后。
We attempted to detect circulating tumor DNA (ctDNA), taking advantage of molecular barcode next-generation sequencing (MB-NGS), which can be more easily customized to detect a variety of mutations with a high sensitivity than PCR-based methods. Sequencing with a gene panel consisting of the 13 most frequently mutated genes in breast tumors from stage I or II patients revealed 95 somatic mutations in the 12 genes in 62% (62/100) of tumors. Then, plasma DNA from each patient (n = 62) before surgery was analyzed via MB-NGS customized to each somatic mutation, resulting in the detection of ctDNA in 16.1% (10/62) of patients. ctDNA was significantly associated with biologically aggressive phenotypes, including large tumor size (P = .004), positive lymph node (P = .009), high histological grade (P < .001), negative ER (P = .018), negative PR (P = .017), and positive HER2 (P = .046). Furthermore, distant disease-free survival was significantly worse in patients with ctDNA (n = 10) than those without ctDNA (n = 52) (P < .001). Our results demonstrate that MB-NGS personalized to each mutation can detect ctDNA with a high sensitivity in early breast cancer patients at diagnosis, and it seems to have a potential to serve as a clinically useful tumor marker for predicting their prognosis.