Adalsteinsson VA, Ha G, Freeman SS, Choudhury AD, Stover DG, Parsons HA, Gydush G, Reed SC, Rotem D, Rhoades J, et al. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nat Commun. 2017;8:1324.
NOTES
Adalsteinsson, Viktor AHa, GavinFreeman, Samuel SChoudhury, Atish DStover, Daniel GParsons, Heather AGydush, GregoryReed, Sarah CRotem, DenisseRhoades, JustinLoginov, DenisLivitz, DimitriRosebrock, DanielLeshchiner, IgnatyKim, JaegilStewart, ChipRosenberg, MaraFrancis, Joshua MZhang, Cheng-ZhongCohen, OfirOh, CoyinDing, HuimingPolak, PazLloyd, MaxMahmud, SairahHelvie, KarlaMerrill, Margaret SSantiago, Rebecca AO'Connor, Edward PJeong, Seong HLeeson, RachelBarry, Rachel MKramkowski, Joseph FZhang, ZhenweiPolacek, LauraLohr, Jens GSchleicher, MollyLipscomb, EmilySaltzman, AndreaOliver, Nelly MMarini, LoriWaks, Adrienne GHarshman, Lauren CTolaney, Sara MVan Allen, Eliezer MWiner, Eric PLin, Nancy UNakabayashi, MariTaplin, Mary-EllenJohannessen, Cory MGarraway, Levi AGolub, Todd RBoehm, Jesse SWagle, NikhilGetz, GadLove, J ChristopherMeyerson, MatthewengK08 CA191026/CA/NCI NIH HHS/P30 CA014051/CA/NCI NIH HHS/MFE-140389/CIHR/CanadaResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tEnglandNat Commun. 2017 Nov 6;8(1):1324. doi: 10.1038/s41467-017-00965-y.
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 0.1x 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.
Last updated on 02/17/2021