Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS.
Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS.
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DOI：
10.1038/s41467-021-24109-5
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发表时间：
2021-06-18
影响因子：
16.6
通讯作者：
Benayed R
中科院分区：
文献类型：
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作者：
Rose Brannon A;Jayakumaran G;Diosdado M;Patel J;Razumova A;Hu Y;Meng F;Haque M;Sadowska J;Murphy BJ;Baldi T;Johnson I;Ptashkin R;Hasan M;Srinivasan P;Rema AB;Rijo I;Agarunov A;Won H;Perera D;Brown DN;Samoila A;Jing X;Gedvilaite E;Yang JL;Stephens DP;Dix JM;DeGroat N;Nafa K;Syed A;Li A;Lebow ES;Bowman AS;Ferguson DC;Liu Y;Mata DA;Sharma R;Yang SR;Bale T;Benhamida JK;Chang JC;Dogan S;Hameed MR;Hechtman JF;Moung C;Ross DS;Vakiani E;Vanderbilt CM;Yao J;Razavi P;Smyth LM;Chandarlapaty S;Iyer G;Abida W;Harding JJ;Krantz B;O'Reilly E;Yu HA;Li BT;Rudin CM;Diaz L;Solit DB;Arcila ME;Ladanyi M;Loomis B;Tsui D;Berger MF;Zehir A;Benayed R
从癌症患者血浆中提取的循环中的无细胞DNA可用于非侵入性询问体细胞肿瘤的改变。在这里，我们开发了MSK-ACCESS(纪念斯隆-凯特林-循环cfDNA分析以检查体细胞状态)，一种NGS分析，用于检测129个基因中的极低频率体细胞变化。分析验证表明，92%的灵敏度在从头突变中预测到0.5%的等位基因频率，99%的灵敏度在先验突变谱中。为了评估MSK-Access的性能，我们报告了681份预期血液样本的结果，这些样本经过了临床分析，以指导患者管理。在73%的样本中检测到躯体变化，其中56%具有临床上可操作的变化。利用匹配的正常测序可以保留体细胞变化，同时删除10,000多个生殖系和克隆性造血变异体。我们的经验说明了在解释cfDNA结果时分析匹配的正常样本的重要性，并强调了cfDNA作为癌症患者基因组图谱来源的重要性。液体活组织检查可以非侵入性地检测肿瘤的体细胞突变。在这里，作者开发并测试了MSK-Access，这是一种基于NGS的临床测试，用于识别129个基因的低频突变，并描述了它如何使临床患者受益。
Circulating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulating cfDNA to Examine Somatic Status), an NGS assay for detection of very low frequency somatic alterations in 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 99% for a priori mutation profiling. To evaluate the performance of MSK-ACCESS, we report results from 681 prospective blood samples that underwent clinical analysis to guide patient management. Somatic alterations are detected in 73% of the samples, 56% of which have clinically actionable alterations. The utilization of matched normal sequencing allows retention of somatic alterations while removing over 10,000 germline and clonal hematopoiesis variants. Our experience illustrates the importance of analyzing matched normal samples when interpreting cfDNA results and highlights the importance of cfDNA as a genomic profiling source for cancer patients. Liquid biopsies allow the non-invasive detection of somatic mutations from tumours. Here, the authors develop and test MSK-ACCESS, an NGS-based clinical assay for identifying low frequency mutations in 129 genes and describe how it benefits patients in the clinic.
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影响因子：
12.3
作者：
Mayrhofer M;De Laere B;Whitington T;Van Oyen P;Ghysel C;Ampe J;Ost P;Demey W;Hoekx L;Schrijvers D;Brouwers B;Lybaert W;Everaert E;De Maeseneer D;Strijbos M;Bols A;Fransis K;Oeyen S;van Dam PJ;Van den Eynden G;Rutten A;Aly M;Nordström T;Van Laere S;Rantalainen M;Rajan P;Egevad L;Ullén A;Yachnin J;Dirix L;Grönberg H;Lindberg J
通讯作者：
Lindberg J
影响因子：
16.6
作者：
Chabon JJ;Simmons AD;Lovejoy AF;Esfahani MS;Newman AM;Haringsma HJ;Kurtz DM;Stehr H;Scherer F;Karlovich CA;Harding TC;Durkin KA;Otterson GA;Purcell WT;Camidge DR;Goldman JW;Sequist LV;Piotrowska Z;Wakelee HA;Neal JW;Alizadeh AA;Diehn M
通讯作者：
Diehn M
影响因子：
16.6
作者：
Leal, Alessandro;van Grieken, Nicole C. T.;Velculescu, Victor E.
通讯作者：
Velculescu, Victor E.
影响因子：
28.4
作者：
Reinert, Thomas;Henriksen, Tenna Vesterman;Andersen, Claus Lindbjerg
通讯作者：
Andersen, Claus Lindbjerg
影响因子：
--
作者：
Mehrotra M;Singh RR;Loghavi S;Duose DY;Barkoh BA;Behrens C;Patel KP;Routbort MJ;Kopetz S;Broaddus RR;Medeiros LJ;Wistuba II;Luthra R
通讯作者：
Luthra R