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【NEJM】血循环中肺癌细胞的EGFR突变的检测意义
ABSTRACT
Background The use of tyrosine kinase inhibitors to target the epidermal growth factor receptor gene (EGFR) in patients with non–small-cell lung cancer is effective but limited by the emergence of drug-resistance mutations. Molecular characterization of circulating tumor cells may provide a strategy for noninvasive serial monitoring of tumor genotypes during treatment.
Methods We captured highly purified circulating tumor cells from the blood of patients with non–small-cell lung cancer using a microfluidic device containing microposts coated with antibodies against epithelial cells. We performed EGFR mutational analysis on DNA recovered from circulating tumor cells using allele-specific polymerase-chain-reaction amplification and compared the results with those from concurrently isolated free plasma DNA and from the original tumor-biopsy specimens.
Results We isolated circulating tumor cells from 27 patients with metastatic non–small-cell lung cancer (median number, 74 cells per milliliter). We identified the expected EGFR activating mutation in circulating tumor cells from 11 of 12 patients (92%) and in matched free plasma DNA from 4 of 12 patients (33%) (P=0.009). We detected the T790M mutation, which confers drug resistance, in circulating tumor cells collected from patients with EGFR mutations who had received tyrosine kinase inhibitors. When T790M was detectable in pretreatment tumor-biopsy specimens, the presence of the mutation correlated with reduced progression-free survival (7.7 months vs. 16.5 months, P<0.001). Serial analysis of circulating tumor cells showed that a reduction in the number of captured cells was associated with a radiographic tumor response; an increase in the number of cells was associated with tumor progression, with the emergence of additional EGFR mutations in some cases.
Conclusions Molecular analysis of circulating tumor cells from the blood of patients with lung cancer offers the possibility of monitoring changes in epithelial tumor genotypes during the course of treatment.
http://intl-content.nejm.org/cgi/content/abstract/359/4/366 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Detection of Mutations in EGFR in Circulating Lung-Cancer Cells
循环中肺癌细胞的EGFR突变的检测
摘要
Background The use of tyrosine kinase inhibitors to target the epidermal growth factor receptor gene (EGFR) in patients with non–small-cell lung cancer is effective but limited by the emergence of drug-resistance mutations. Molecular characterization of circulating tumor cells may provide a strategy for noninvasive serial monitoring of tumor genotypes during treatment.
背景：用针对EGFR的酪氨酸激酶抑制剂靶向治疗非小细胞肺癌是有效的治疗方法，但是由于抗药性的出现而疗效受到了限制。然而，通过对循环中肿瘤细胞的分子特征分析，提供了一种非侵入性的方法连续的检测在治疗过程中肿瘤的基因型变化过程。
Methods We captured highly purified circulating tumor cells from the blood of patients with non–small-cell lung cancer using a microfluidic device containing microposts coated with antibodies against epithelial cells. We performed EGFR mutational analysis on DNA recovered from circulating tumor cells using allele-specific polymerase-chain-reaction amplification and compared the results with those from concurrently isolated free plasma DNA and from the original tumor-biopsy specimens.
方法：在非小细胞肺癌患者中，我们用铺有针对上皮细胞抗体的微流体装置
捕获循环中的肿瘤细胞。我们用（allele-specific polymerase-chain-reaction ）等位基因特异性PCR扩增从循环肿瘤细胞中提取出来的DNA，来检测EGFR的突变，并同时与外周血浆游离DNA和从原发肿瘤活检组织标本的DNA样品相比较。
Results We isolated circulating tumor cells from 27 patients with metastatic non–small-cell lung cancer (median number, 74 cells per milliliter).
结果：我们从27名转移的非小细胞肺癌患者中分离了循环肿瘤细胞（平均为每升74个细胞）
We identified the expected EGFR activating mutation in circulating tumor cells from 11 of 12 patients (92%) and in matched free plasma DNA from 4 of 12 patients (33%) (P=0.009).
我们从12名患者中鉴定出了11名(92%) 有有期待中的EGRF激活性突变，在相对应的无血浆DNA中，发现了4例(33%) (P=0.009)。
We detected the T790M mutation, which confers drug resistance, in circulating tumor cells collected from patients with EGFR mutations who had received tyrosine kinase inhibitors.
在从接受酪氨酸激酶抑制剂治疗患者中收集的循环肿瘤细胞中，我们检测到了引起耐药的T790M突变，
When T790M was detectable in pretreatment tumor-biopsy specimens, the presence of the mutation correlated with reduced progression-free survival (7.7 months vs. 16.5 months, P<0.001).
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作者:admin@医学,生命科学 2011-04-26 05:14
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