Liquid biopsy-based comprehensive gene mutation profiling for gynecological cancer using CAncer Personalized Profiling by deep Sequencing
Liquid biopsy-based comprehensive gene mutation profiling for gynecological cancer using CAncer Personalized Profiling by deep Sequencing
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DOI：
10.1038/s41598-019-47030-w
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发表时间：
2019-07-18
影响因子：
4.6
通讯作者：
Ino, Kazuhiko
中科院分区：
文献类型：
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作者：
Iwahashi, Naoyuki;Sakai, Kazuko;Ino, Kazuhiko
循环肿瘤 DNA (ctDNA) 的液体活检最近已被用作检测肿瘤特异性突变的非侵入性诊断工具。我们提出了一项针对妇科癌症的 ctDNA 液体活检的研究，该研究使用超灵敏的基于下一代测序的 ctDNA 检测方法，称为 CAncer 深度测序个性化分析 (CAPP-Seq)。我们对从 16 名妇科癌症患者身上获得的血浆 ctDNA 进行了 CAPP-Seq。在所有情况下，ctDNA 中至少检测到一种非同义体细胞突变。在治疗前 ctDNA 中，16、4/16、5/16、2/16、2/16 和 2/16 名患者中的 4 名分别具有 TP53、KRAS、APC、PIK3CA、BRCA1 和 EGFR 突变。在 16 名患者中的 2 名患者的 ctDNA 中检测到 MET 基因拷贝数增加，配对肿瘤样本的 FISH 分析证实了这些结果。在 2 名接受新辅助化疗的卵巢癌患者中，基因突变模式的变化与治疗反应相关。这些发现表明，基于 CAPP-Seq 的液体活检可用于高频独立妇科癌症的遗传表征，并可能在临床上用于非侵入性肿瘤基因分型和治疗反应监测。
Liquid biopsies of circulating tumor DNA (ctDNA) have recently been used as a non-invasive diagnostic tool for detecting tumor-specific mutations. We present a study of ctDNA liquid biopsies in gynecological cancer using an ultrasensitive next-generation sequencing-based method for ctDNA detection named CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). We performed CAPP-Seq with plasma-ctDNA obtained from 16 patients with gynecological cancer. In all cases, at least one non-synonymous somatic mutation was detected in the ctDNA. In the pre-treatment ctDNA, 4 of 16, 4/16, 5/16, 2/16, 2/16, and 2/16 patients had TP53, KRAS, APC, PIK3CA, BRCA1, and EGFR mutations, respectively. MET gene copy-number gains were detected in the ctDNA of 2 of 16 patients, and FISH analysis of the paired tumor samples confirmed these results. In 2 neoadjuvant chemotherapy-treated ovarian cancer patients, the changes in gene mutation patterns were associated with the treatment response. These findings suggest that CAPP-Seq-based liquid biopsies can be used for the genetic characterization of independent gynecological cancers with high frequency, and might be clinically useful for non-invasive tumor genotyping and therapeutic response monitoring.