5月30日，國際著名雜志Science Translational Medicine在線刊登的一項新的研究報告中指出，一種新的基因測序技術可能比用傳統(tǒng)的腫瘤活檢來發(fā)現(xiàn)癌性突變更安全及廉價,。
這種叫做"TAm-Seq"的技術可通過收集血漿中循環(huán)的DNA片段，放大那些與癌癥相關聯(lián)的DNA部分并深入挖掘基因序列來發(fā)現(xiàn)那些難以辨認的突變,。
Tim Forshew及其同事分析了來自于一組晚期卵巢癌癥病人的腫瘤樣本并發(fā)現(xiàn),，有67%的病人帶有腫瘤抑制基因TP53的突變。該團隊還發(fā)現(xiàn),，至少在其疾病發(fā)展過程中的某一時刻,，卵巢癌癥病人大約有2%的DNA含有腫瘤特異性突變,。這些發(fā)現(xiàn)提示，TAm-Seq可能是一種非侵入性的工具,，是一種可幫助醫(yī)生發(fā)現(xiàn)腫瘤中未知突變的“液體活檢”,。這種技術還可被用來監(jiān)測新型癌性突變的出現(xiàn)。（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.
