Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors
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Adalsteinsson_et_al-2017-Nature_Communications.pdf
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Author(s)
Ha, Gavin
Freeman, Samuel S.
Choudhury, Atish D.
Stover, Daniel G.
Parsons, Heather A.
Gydush, Gregory
Reed, Sarah C.
Rotem, Denisse
Rhoades, Justin
Livitz, Dimitri
Date Issued
November 2017
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Adalsteinsson, Viktor A. et al. “Scalable Whole-Exome Sequencing of Cell-Free DNA Reveals High Concordance with Metastatic Tumors.” Nature Communications 8, 1 (November 2017): 1324 © 2017 The Author(s)
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International
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DOI of Published Version
https://doi.org/10.1038/s41467-017-00965-y
