Title |
Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors
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Published in |
Nature Communications, November 2017
|
DOI | 10.1038/s41467-017-00965-y |
Pubmed ID | |
Authors |
Viktor A. Adalsteinsson, Gavin Ha, Samuel S. Freeman, Atish D. Choudhury, Daniel G. Stover, Heather A. Parsons, Gregory Gydush, Sarah C. Reed, Denisse Rotem, Justin Rhoades, Denis Loginov, Dimitri Livitz, Daniel Rosebrock, Ignaty Leshchiner, Jaegil Kim, Chip Stewart, Mara Rosenberg, Joshua M. Francis, Cheng-Zhong Zhang, Ofir Cohen, Coyin Oh, Huiming Ding, Paz Polak, Max Lloyd, Sairah Mahmud, Karla Helvie, Margaret S. Merrill, Rebecca A. Santiago, Edward P. O’Connor, Seong H. Jeong, Rachel Leeson, Rachel M. Barry, Joseph F. Kramkowski, Zhenwei Zhang, Laura Polacek, Jens G. Lohr, Molly Schleicher, Emily Lipscomb, Andrea Saltzman, Nelly M. Oliver, Lori Marini, Adrienne G. Waks, Lauren C. Harshman, Sara M. Tolaney, Eliezer M. Van Allen, Eric P. Winer, Nancy U. Lin, Mari Nakabayashi, Mary-Ellen Taplin, Cory M. Johannessen, Levi A. Garraway, Todd R. Golub, Jesse S. Boehm, Nikhil Wagle, Gad Getz, J. Christopher Love, Matthew Meyerson |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 85 | 38% |
United Kingdom | 11 | 5% |
Saudi Arabia | 6 | 3% |
Canada | 6 | 3% |
France | 5 | 2% |
Spain | 5 | 2% |
Germany | 3 | 1% |
India | 3 | 1% |
Switzerland | 3 | 1% |
Other | 23 | 10% |
Unknown | 71 | 32% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 109 | 49% |
Members of the public | 91 | 41% |
Practitioners (doctors, other healthcare professionals) | 16 | 7% |
Science communicators (journalists, bloggers, editors) | 4 | 2% |
Unknown | 1 | <1% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 717 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 163 | 23% |
Student > Ph. D. Student | 111 | 15% |
Student > Master | 57 | 8% |
Other | 49 | 7% |
Student > Bachelor | 46 | 6% |
Other | 94 | 13% |
Unknown | 197 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 172 | 24% |
Medicine and Dentistry | 128 | 18% |
Agricultural and Biological Sciences | 85 | 12% |
Computer Science | 26 | 4% |
Engineering | 16 | 2% |
Other | 70 | 10% |
Unknown | 220 | 31% |