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Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors

Adalsteinsson, Viktor A ; Ha, Gavin ; Freeman, Samuel S ; Choudhury, Atish D ; Stover, Daniel G ; Parsons, Heather A ; Gydush, Gregory ; Reed, Sarah C ; Rotem, Denisse ; Rhoades, Justin ; Loginov, Denis ; Livitz, Dimitri ; Rosebrock, Daniel ; Leshchiner, Ignaty ; Kim, Jaegil ; Stewart, Chip ; Rosenberg, Mara ; Francis, Joshua M ; Zhang, Cheng-Zhong ; Cohen, Ofir ; Oh, Coyin ; Ding, Huiming ; Polak, Paz ; Lloyd, Max ; Mahmud, Sairah ; Helvie, Karla ; Merrill, Margaret S ; Santiago, Rebecca A ; O’Connor, Edward P ; Jeong, Seong H ; Leeson, Rachel ; Barry, Rachel M ; Kramkowski, Joseph F ; Zhang, Zhenwei ; Polacek, Laura ; Lohr, Jens G ; Schleicher, Molly ; Lipscomb, Emily ; Saltzman, Andrea ; Oliver, Nelly M ; Marini, Lori ; Waks, Adrienne G ; Harshman, Lauren C ; Tolaney, Sara M ; Van Allen, Eliezer M ; Winer, Eric P ; Lin, Nancy U ; Nakabayashi, Mari ; Taplin, Mary-Ellen ; Johannessen, Cory M ; Garraway, Levi A ; Golub, Todd R ; Boehm, Jesse S ; Wagle, Nikhil ; Getz, Gad ; Love, J. Christopher ; Meyerson, Matthew

Nature Publishing Group UK 2017

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Título:
Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors
Autor: Adalsteinsson, Viktor A ; Ha, Gavin ; Freeman, Samuel S ; Choudhury, Atish D ; Stover, Daniel G ; Parsons, Heather A ; Gydush, Gregory ; Reed, Sarah C ; Rotem, Denisse ; Rhoades, Justin ; Loginov, Denis ; Livitz, Dimitri ; Rosebrock, Daniel ; Leshchiner, Ignaty ; Kim, Jaegil ; Stewart, Chip ; Rosenberg, Mara ; Francis, Joshua M ; Zhang, Cheng-Zhong ; Cohen, Ofir ; Oh, Coyin ; Ding, Huiming ; Polak, Paz ; Lloyd, Max ; Mahmud, Sairah ; Helvie, Karla ; Merrill, Margaret S ; Santiago, Rebecca A ; O’Connor, Edward P ; Jeong, Seong H ; Leeson, Rachel ; Barry, Rachel M ; Kramkowski, Joseph F ; Zhang, Zhenwei ; Polacek, Laura ; Lohr, Jens G ; Schleicher, Molly ; Lipscomb, Emily ; Saltzman, Andrea ; Oliver, Nelly M ; Marini, Lori ; Waks, Adrienne G ; Harshman, Lauren C ; Tolaney, Sara M ; Van Allen, Eliezer M ; Winer, Eric P ; Lin, Nancy U ; Nakabayashi, Mari ; Taplin, Mary-Ellen ; Johannessen, Cory M ; Garraway, Levi A ; Golub, Todd R ; Boehm, Jesse S ; Wagle, Nikhil ; Getz, Gad ; Love, J. Christopher ; Meyerson, Matthew
Notas: Nature Communications
doi:10.1038/s41467-017-00965-y
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673918/pdf/
Descrição: 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.
Editor: Nature Publishing Group UK
Data de criação/publicação: 2017
Idioma: Inglês

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Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors

Nature Publishing Group UK 2017

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