Sci Transl Med：“液体活检”可捕捉癌性突变

5月30日，国际著名杂志Science Translational Medicine在线刊登的一项新的研究报告中指出，一种新的基因测序技术可能比用传统的肿瘤活检来发现癌性突变更安全及廉价。

这种叫做"TAm-Seq"的技术可通过收集血浆中循环的DNA片段，放大那些与癌症相关联的DNA部分并深入挖掘基因序列来发现那些难以辨认的突变。

Tim Forshew及其同事分析了来自于一组晚期卵巢癌症病人的肿瘤样本并发现，有67%的病人带有肿瘤抑制基因TP53的突变。该团队还发现，至少在其疾病发展过程中的某一时刻，卵巢癌症病人大约有2%的DNA含有肿瘤特异性突变。这些发现提示，TAm-Seq可能是一种非侵入性的工具，是一种可帮助医生发现肿瘤中未知突变的“液体活检”。这种技术还可被用来监测新型癌性突变的出现。（生物谷Bioon.com）

doi:10.1126/scitranslmed.3003726
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Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA

Tim Forshew1,*, Muhammed Murtaza1,2,*, Christine Parkinson1,2,3,*, Davina Gale1,*, Dana W. Y. Tsui1,*, Fiona Kaper4,†, Sarah-Jane Dawson1,2,3, Anna M. Piskorz1,2, Mercedes Jimenez-Linan3,5, David Bentley6, James Hadfield1, Andrew P. May4, Carlos Caldas1,2,3,7, James D. Brenton1,2,3,7,‡ and Nitzan Rosenfeld1,2,‡

Plasma of cancer patients contains cell-free tumor DNA that carries information on tumor mutations and tumor burden. Individual mutations have been probed using allele-specific assays, but sequencing of entire genes to detect cancer mutations in circulating DNA has not been demonstrated. We developed a method for tagged-amplicon deep sequencing (TAm-Seq) and screened 5995 genomic bases for low-frequency mutations. Using this method, we identified cancer mutations present in circulating DNA at allele frequencies as low as 2%, with sensitivity and specificity of >97%. We identified mutations throughout the tumor suppressor gene TP53 in circulating DNA from 46 plasma samples of advanced ovarian cancer patients. We demonstrated use of TAm-Seq to noninvasively identify the origin of metastatic relapse in a patient with multiple primary tumors. In another case, we identified in plasma an EGFR mutation not found in an initial ovarian biopsy. We further used TAm-Seq to monitor tumor dynamics, and tracked 10 concomitant mutations in plasma of a metastatic breast cancer patient over 16 months. This low-cost, high-throughput method could facilitate analysis of circulating DNA as a noninvasive “liquid biopsy” for personalized cancer genomics.