Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.
Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.
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无细胞DNA的可扩展全外显子组测序显示与转移性肿瘤高度一致。
DOI：
10.1038/s41467-017-00965-y
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发表时间：
2017-11-06
影响因子：
16.6
通讯作者：
Meyerson M
中科院分区：
文献类型：
--
作者：
Adalsteinsson VA;Ha G;Freeman SS;Choudhury AD;Stover DG;Parsons HA;Gydush G;Reed SC;Rotem D;Rhoades J;Loginov D;Livitz D;Rosebrock D;Leshchiner I;Kim J;Stewart C;Rosenberg M;Francis JM;Zhang CZ;Cohen O;Oh C;Ding H;Polak P;Lloyd M;Mahmud S;Helvie K;Merrill MS;Santiago RA;O'Connor EP;Jeong SH;Leeson R;Barry RM;Kramkowski JF;Zhang Z;Polacek L;Lohr JG;Schleicher M;Lipscomb E;Saltzman A;Oliver NM;Marini L;Waks AG;Harshman LC;Tolaney SM;Van Allen EM;Winer EP;Lin NU;Nakabayashi M;Taplin ME;Johannessen CM;Garraway LA;Golub TR;Boehm JS;Wagle N;Getz G;Love JC;Meyerson M
无细胞DNA（cfDNA）的全外显子组测序可以实现来自血液的肿瘤的全面分析，但是cfDNA和肿瘤活检之间的全基因组一致性是不确定的。在这里，我们报告了ichorCNA，这是一种软件，可以在事先不知道肿瘤突变的情况下，从0.1×覆盖率的全基因组测序数据中定量cfDNA中的肿瘤含量。我们将ichorCNA应用于520例转移性前列腺癌或乳腺癌患者的1439份血液样本。在每个患者的最早测试样品中，34%的患者具有≥10%的肿瘤来源的cfDNA，足以进行标准覆盖全外显子组测序。使用全外显子组测序，我们验证了来自41名cfDNA肿瘤含量≥10%的患者的cfDNA和匹配的肿瘤活检组织之间的克隆体细胞突变（88%）、拷贝数改变（80%）、突变特征和新抗原的一致性。总之，我们提供了鉴定适合进行全面cfDNA谱分析的患者的方法，揭示了其对许多患者的适用性，并证明了cfDNA和转移性肿瘤全外显子组测序的高度一致性。从血液中的无细胞DNA中识别肿瘤的突变景观可能有助于癌症的诊断。在这里，作者介绍了ichorCNA，一种定量无细胞DNA中肿瘤含量的软件，他们证明了无细胞DNA全外显子组测序与转移性肿瘤全外显子组测序是一致的。
Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing. Identifying the mutational landscape of tumours from cell-free DNA in the blood could help diagnostics in cancer. Here, the authors present ichorCNA, software that quantifies tumour content in cell free DNA, and they demonstrate that cell-free DNA whole-exome sequencing is concordant with metastatic tumour whole-exome sequencing.
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影响因子：
7
作者：
Ha G;Roth A;Lai D;Bashashati A;Ding J;Goya R;Giuliany R;Rosner J;Oloumi A;Shumansky K;Chin SF;Turashvili G;Hirst M;Caldas C;Marra MA;Aparicio S;Shah SP
通讯作者：
Shah SP
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
7
作者：
Ha G;Roth A;Khattra J;Ho J;Yap D;Prentice LM;Melnyk N;McPherson A;Bashashati A;Laks E;Biele J;Ding J;Le A;Rosner J;Shumansky K;Marra MA;Gilks CB;Huntsman DG;McAlpine JN;Aparicio S;Shah SP
通讯作者：
Shah SP
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel