| Literature DB >> 32483360 |
Asaf Zviran1,2, Rafael C Schulman1,2, Minita Shah1, Steven T K Hill1,2, Sunil Deochand1,2, Cole C Khamnei1,2, Dillon Maloney1, Kristofer Patel1,2, Will Liao1, Adam J Widman1,2,3, Phillip Wong3, Margaret K Callahan3, Gavin Ha4, Sarah Reed5, Denisse Rotem5, Dennie Frederick6, Tatyana Sharova6, Benchun Miao6, Tommy Kim6, Greg Gydush5, Justin Rhoades5, Kevin Y Huang1,2, Nathaniel D Omans1,2, Patrick O Bolan2, Andrew H Lipsky2, Chelston Ang1,2, Murtaza Malbari2, Catherine F Spinelli2, Selena Kazancioglu1, Alexi M Runnels1, Samantha Fennessey1, Christian Stolte1, Federico Gaiti1,2, Giorgio G Inghirami2, Viktor Adalsteinsson5, Brian Houck-Loomis1, Jennifer Ishii1, Jedd D Wolchok3, Genevieve Boland6, Nicolas Robine1, Nasser K Altorki2, Dan A Landau7,8.
Abstract
In many areas of oncology, we lack sensitive tools to track low-burden disease. Although cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low-disease-burden monitoring through the prevailing deep targeted sequencing paradigm. We reasoned that breadth may supplant depth of sequencing to overcome the barrier of cfDNA abundance. Whole-genome sequencing (WGS) of cfDNA allowed ultra-sensitive detection, capitalizing on the cumulative signal of thousands of somatic mutations observed in solid malignancies, with TF detection sensitivity as low as 10-5. The WGS approach enabled dynamic tumor burden tracking and postoperative residual disease detection, associated with adverse outcome. Thus, we present an orthogonal framework for cfDNA cancer monitoring via genome-wide mutational integration, enabling ultra-sensitive detection, overcoming the limitation of cfDNA abundance and empowering treatment optimization in low-disease-burden oncology care.Entities:
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Year: 2020 PMID： 32483360 PMCID： PMC8108131 DOI： 10.1038/s41591-020-0915-3
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440