Tumor volume determines the feasibility of cell-free DNA sequencing for mutation detection in non-small cell lung cancer.
Tumor volume determines the feasibility of cell-free DNA sequencing for mutation detection in non-small cell lung cancer.
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DOI：
10.1111/cas.13068
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发表时间：
2016-11
期刊：
影响因子：
5.7
通讯作者：
Ikeda N
中科院分区：
文献类型：
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作者：
Ohira T;Sakai K;Matsubayashi J;Kajiwara N;Kakihana M;Hagiwara M;Hibi M;Yoshida K;Maeda J;Ohtani K;Nagao T;Nishio K;Ikeda N
下一代测序(NGS)和数字聚合酶链式反应技术可以分析晚期肺癌患者循环中无细胞DNA(CfDNA)的突变情况。我们现在已经评估了cfDNA测序用于早期非小细胞肺癌患者突变检测的可行性。共收集150份来自IA-IIIA期非小细胞肺癌患者的匹配肿瘤和血清样本。从肿瘤组织提取的DNA扩增序列检测到EGFR(37%的患者)、TP53(39%)和KRAS(10%)的频繁突变，与先前的发现一致。相反，尽管提取了足够量的cfDNA(中位数为4936拷贝/毫升血清)，cfDNA的NGS仅在3例、5例和1例患者中发现了EGFR、TP53和PIK3CA突变。下一代测序检测cfDNA突变的准确率较高(98.8%)，提示cfDNA突变频率低并非由于检测灵敏度低所致。虽然cfDNA的产量在不同的肿瘤分期中没有差异，但在7例患者中发现了cfDNA突变，这些突变发生在IIA-IIIA期以及T2b或T3期。在T2b-T4期，cfDNA突变阳性患者的肿瘤体积显著高于阴性患者(159.1±58.0vs.52.5±9.9cm3，P=0.014)。因此，我们的结果表明，肿瘤体积是以cfDNA为分析物进行突变检测的可行性的决定因素。
Next‐generation sequencing (NGS) and digital PCR technologies allow analysis of the mutational profile of circulating cell‐free DNA (cfDNA) in individuals with advanced lung cancer. We have now evaluated the feasibility of cfDNA sequencing for mutation detection in patients with non‐small cell lung cancer at earlier stages. A total of 150 matched tumor and serum samples were collected from non‐small cell lung cancer patients at stages IA–IIIA. Amplicon sequencing with DNA extracted from tumor tissue detected frequent mutations in EGFR (37% of patients), TP53 (39%), and KRAS (10%), consistent with previous findings. In contrast, NGS of cfDNA identified only EGFR,TP53, and PIK3CA mutations in three, five, and one patient, respectively, even though adequate amounts of cfDNA were extracted (median of 4936 copies/mL serum). Next‐generation sequencing showed a high accuracy (98.8%) compared with droplet digital PCR for cfDNA mutation detection, suggesting that the low frequency of mutations in cfDNA was not due to a low assay sensitivity. Whereas the yield of cfDNA did not differ among tumor stages, the cfDNA mutations were detected in seven patients at stages IIA–IIIA and at T2b or T3. Tumor volume was significantly higher in the cfDNA mutation‐positive patients than in the negative patients at stages T2b–T4 (159.1 ± 58.0 vs. 52.5 ± 9.9 cm3, P = 0.014). Our results thus suggest that tumor volume is a determinant of the feasibility of mutation detection with cfDNA as the analyte.
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影响因子：
--
作者：
Okamoto I;Sakai K;Morita S;Yoshioka H;Kaneda H;Takeda K;Hirashima T;Kogure Y;Kimura T;Takahashi T;Atagi S;Seto T;Sawa T;Yamamoto M;Satouchi M;Okuno M;Nagase S;Takayama K;Tomii K;Maeda T;Oizumi S;Fujii S;Akashi Y;Nishino K;Ebi N;Nakagawa K;Nakanishi Y;Nishio K
通讯作者：
Nishio K
影响因子：
--
作者：
Ishii H;Azuma K;Sakai K;Kawahara A;Yamada K;Tokito T;Okamoto I;Nishio K;Hoshino T
通讯作者：
Hoshino T
影响因子：
11.5
作者：
Lee, Young Joo;Yoon, Kyong-Ah;Lee, Jin Soo
通讯作者：
Lee, Jin Soo
影响因子：
11.5
作者：
Taniguchi, Kazuya;Uchida, Junji;Kato, Kikuya
通讯作者：
Kato, Kikuya
影响因子：
3.7
作者：
Narahara, Maiko;Higasa, Koichiro;Yamada, Ryo
通讯作者：
Yamada, Ryo