Whole exome sequencing for determination of tumor mutation load in liquid biopsy from advanced cancer patients.
Whole exome sequencing for determination of tumor mutation load in liquid biopsy from advanced cancer patients.
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DOI：
10.1371/journal.pone.0188174
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Lacroix L
中科院分区：
文献类型：
--
作者：
Koeppel F;Blanchard S;Jovelet C;Genin B;Marcaillou C;Martin E;Rouleau E;Solary E;Soria JC;André F;Lacroix L
在几项研究中，肿瘤突变负荷（TML）已被提出作为患者对免疫治疗反应的生物标志物。TML通常通过肿瘤活检DNA（tDNA）全外显子组测序（WES）确定，因此TML评估受到活检信息可用性的限制。由液体活检提供的循环无细胞DNA（cfDNA）是用于分子谱分析的活检的替代样本。然而，对来自血浆的DNA进行WES在技术上具有挑战性，并且从液体活检确定肿瘤突变负荷的能力仍有待证明。在本研究中，对来自32名不同癌症类型的转移性患者的cfDNA进行了WES，这些患者被纳入了MOSCATO 01（NCT 01566019）和/或MATLAND（NCT 02517892）分子分类试验。将对cfDNA进行的靶向基因测序（TGS）和WES的结果与肿瘤组织活检的结果进行比较。在cfDNA样品中，与靶向测序（TGS）相比，WES突变检测灵敏度为92%。当比较cfDNA-WES与tDNA-WES时，突变检测灵敏度为53%，与先前发表的比较cfDNA-TGS与tDNA-TGS的前瞻性研究一致。对于在cfDNA中确认存在肿瘤DNA的样品，来自液体活检的肿瘤突变负荷与肿瘤活检相关。总之，本研究表明，液体活检可用于确定肿瘤突变负荷。用于解释的液体活检的鉴定是使用cfDNA进行突变负荷估计的关键点。
Tumor mutation load (TML) has been proposed as a biomarker of patient response to immunotherapy in several studies. TML is usually determined by tumor biopsy DNA (tDNA) whole exome sequencing (WES), therefore TML evaluation is limited by informative biopsy availability. Circulating cell free DNA (cfDNA) provided by liquid biopsy is a surrogate specimen to biopsy for molecular profiling. Nevertheless performing WES on DNA from plasma is technically challenging and the ability to determine tumor mutation load from liquid biopsies remains to be demonstrated. In the current study, WES was performed on cfDNA from 32 metastatic patients of various cancer types included into MOSCATO 01 (NCT01566019) and/or MATCHR (NCT02517892) molecular triage trials. Results from targeted gene sequencing (TGS) and WES performed on cfDNA were compared to results from tumor tissue biopsy. In cfDNA samples, WES mutation detection sensitivity was 92% compared to targeted sequencing (TGS). When comparing cfDNA-WES to tDNA-WES, mutation detection sensitivity was 53%, consistent with previously published prospective study comparing cfDNA-TGS to tDNA-TGS. For samples in which presence of tumor DNA was confirmed in cfDNA, tumor mutation load from liquid biopsy was correlated with tumor biopsy. Taken together, this study demonstrated that liquid biopsy may be applied to determine tumor mutation load. Qualification of liquid biopsy for interpretation is a crucial point to use cfDNA for mutational load estimation.
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影响因子：
10.1
作者：
Johnson DB;Frampton GM;Rioth MJ;Yusko E;Xu Y;Guo X;Ennis RC;Fabrizio D;Chalmers ZR;Greenbowe J;Ali SM;Balasubramanian S;Sun JX;He Y;Frederick DT;Puzanov I;Balko JM;Cates JM;Ross JS;Sanders C;Robins H;Shyr Y;Miller VA;Stephens PJ;Sullivan RJ;Sosman JA;Lovly CM
通讯作者：
Lovly CM
影响因子：
9.3
作者：
Chan, K. C. Allen;Jiang, Peiyong;Lo, Y. M. D.
通讯作者：
Lo, Y. M. D.
影响因子：
64.8
作者：
Abbosh C;Birkbak NJ;Wilson GA;Jamal-Hanjani M;Constantin T;Salari R;Le Quesne J;Moore DA;Veeriah S;Rosenthal R;Marafioti T;Kirkizlar E;Watkins TBK;McGranahan N;Ward S;Martinson L;Riley J;Fraioli F;Al Bakir M;Grönroos E;Zambrana F;Endozo R;Bi WL;Fennessy FM;Sponer N;Johnson D;Laycock J;Shafi S;Czyzewska-Khan J;Rowan A;Chambers T;Matthews N;Turajlic S;Hiley C;Lee SM;Forster MD;Ahmad T;Falzon M;Borg E;Lawrence D;Hayward M;Kolvekar S;Panagiotopoulos N;Janes SM;Thakrar R;Ahmed A;Blackhall F;Summers Y;Hafez D;Naik A;Ganguly A;Kareht S;Shah R;Joseph L;Marie Quinn A;Crosbie PA;Naidu B;Middleton G;Langman G;Trotter S;Nicolson M;Remmen H;Kerr K;Chetty M;Gomersall L;Fennell DA;Nakas A;Rathinam S;Anand G;Khan S;Russell P;Ezhil V;Ismail B;Irvin-Sellers M;Prakash V;Lester JF;Kornaszewska M;Attanoos R;Adams H;Davies H;Oukrif D;Akarca AU;Hartley JA;Lowe HL;Lock S;Iles N;Bell H;Ngai Y;Elgar G;Szallasi Z;Schwarz RF;Herrero J;Stewart A;Quezada SA;Peggs KS;Van Loo P;Dive C;Lin CJ;Rabinowitz M;Aerts HJWL;Hackshaw A;Shaw JA;Zimmermann BG;TRACERx consortium;PEACE consortium;Swanton C
通讯作者：
Swanton C
DOI：
10.1126/science.aad0095
发表时间：
2015-10-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Van Allen EM;Miao D;Schilling B;Shukla SA;Blank C;Zimmer L;Sucker A;Hillen U;Foppen MHG;Goldinger SM;Utikal J;Hassel JC;Weide B;Kaehler KC;Loquai C;Mohr P;Gutzmer R;Dummer R;Gabriel S;Wu CJ;Schadendorf D;Garraway LA
通讯作者：
Garraway LA
影响因子：
46.9
作者：
Gnirke A;Melnikov A;Maguire J;Rogov P;LeProust EM;Brockman W;Fennell T;Giannoukos G;Fisher S;Russ C;Gabriel S;Jaffe DB;Lander ES;Nusbaum C
通讯作者：
Nusbaum C