Research Institute, Departments of Thoracic Oncology and Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka, Japan.
Clin Cancer Res. 2011 Dec 15;17(24):7808-15. doi: 10.1158/1078-0432.CCR-11-1712. Epub 2011 Oct 5.
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).
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.
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.
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.
表皮生长因子受体（EGFR）体细胞突变检测目前已成为接受 EGFR 酪氨酸激酶抑制剂（EGFR-TKI）治疗的癌症患者的常规诊断方法。循环肿瘤 DNA 是一种很有前途的无创诊断靶点。我们通过定量检测激活和耐药突变来评估其效用，这些突变通过 BEAMing（珠子、乳液、扩增和磁珠）进行测量。
研究了 23 例 EGFR-TKI 治疗后进展的肺癌患者和 21 例从未接受过 EGFR-TKI 治疗的患者。他们的原发肿瘤被证实存在激活突变。在每位患者的血浆 DNA 中，通过 BEAMing 定量检测相应的原发肿瘤中发现的激活突变和 T790M 耐药突变。
在 44 例患者中的 32 例中（72.7%；95%置信区间[CI]，58.0%-83.6%）检测到了血浆 DNA 中的激活突变。在第一组的 23 例患者中，有 10 例（43.5%；95%CI，25.6%-53.4%）检测到了 T790M 突变。T790M 与激活突变的比例范围为 13.3%-94.0%。血浆 DNA 中突变等位基因分数的分布峰值在 0.1%-1%范围内。
BEAMing 的主要优势在于能够从激活突变的等位基因中计算出 T790M 阳性等位基因的分数。该特征使得能够检测癌细胞中 T790M 突变数量的增加和减少，而不受正常细胞 DNA 污染的影响，这对于监测疾病进展可能很有用。循环肿瘤 DNA 可能成为 EGFR 突变检测的一种替代方法。
