Quantitative Detection of EGFR Mutations in Circulating Tumor DNA Derived from Lung Adenocarcinomas
Quantitative Detection of EGFR Mutations in Circulating Tumor DNA Derived from Lung Adenocarcinomas
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DOI：
10.1158/1078-0432.ccr-11-1712
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发表时间：
2011-12-15
影响因子：
11.5
通讯作者：
Kato, Kikuya
中科院分区：
文献类型：
--
作者：
Taniguchi, Kazuya;Uchida, Junji;Kato, Kikuya
目的：体细胞表皮生长因子受体 (EGFR) 突变检查现已成为使用 EGFR 酪氨酸激酶抑制剂 (EGFR-TKI) 治疗癌症的诊断常规。循环肿瘤 DNA 是无创诊断的一个有前景的目标。我们通过定量检测激活突变和耐药突变来评估其效用，并使用 BEAming（珠子、乳液、扩增和磁性）进行测量。 实验设计：对 23 名 EGFR-TKI 治疗后疾病进展的肺癌患者和 21 名从未接受过 EGFR-TKI 治疗的患者进行了研究。他们的原发肿瘤被证实具有激活突变。在每位患者的血浆DNA中，通过BEAMing对相应原发肿瘤中发现的激活突变和T790M耐药突变进行定量。结果：在44名患者中，有32名在血浆DNA中检测到激活突变[72.7%；72.7%；72.7%]。 95% 置信区间 (CI), 58.0%-83.6%]。第一组 23 名患者中有 10 名检测到 T790M 突变（43.5%；95% CI，25.6%-53.4%）。 T790M与激活突变的比例范围为13.3%至94.0%。血浆DNA中突变等位基因分数的分布峰值在0.1%至1%范围内。结论：BEAMing的主要优点是能够从具有激活突变的等位基因中计算T790M阳性等位基因的分数。无论正常细胞 DNA 污染如何，该功能都能够检测癌细胞中 T790M 突变数量的增加和减少，这可能有助于监测疾病进展。循环肿瘤 DNA 有可能用作 EGFR 突变检测的替代方法。临床癌症研究； 17（24）； 7808-15。 (C) 2011 年 AACR。
Purpose: Examination of somatic epidermal growth factor receptor (EGFR) mutations is now a diagnostic routine for treatment of cancer using EGFR tyrosine kinase inhibitors (EGFR-TKI). Circulating tumor DNA is a promising target for noninvasive diagnostics. We evaluated its utility by quantitatively detecting activating and resistant mutations, which were measured with BEAMing (beads, emulsion, amplification, and magnetics).Experimental Design: Twenty-three patients with lung cancer with progressive disease after EGFR-TKI treatment and 21 patients who had never been treated with EGFR-TKIs were studied. Their primary tumors were confirmed to have activating mutations. In the plasma DNA of each patient, the activating mutation found in the corresponding primary tumor and the T790M resistance mutation were quantified by BEAMing.Results: In 32 of 44 patients, activating mutations were detected in the plasma DNA [72.7%; 95% confidence interval (CI), 58.0%-83.6%]. The T790M mutation was detected in 10 of 23 patients in the first group (43.5%; 95% CI, 25.6%-53.4%). The ratio of T790M to activating mutations ranged from 13.3% to 94.0%. The peak of the distribution of the mutation allele fraction in the plasma DNA was in the 0.1% to 1% range.Conclusions: The major advantage of BEAMing is its ability to calculate the fraction of T790M-positive alleles from the alleles with activating mutations. This feature enables the detection of increases and decreases in the number of T790M mutations in cancer cells, regardless of normal cell DNA contamination, which may be useful for monitoring disease progression. Circulating tumor DNA could potentially be used as an alternative method for EGFR mutation detection. Clin Cancer Res; 17(24); 7808-15. (C) 2011 AACR.