Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring.

Autor: Zviran A; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Schulman RC; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Shah M; New York Genome Center, New York, NY, USA., Hill STK; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Deochand S; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Khamnei CC; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Maloney D; New York Genome Center, New York, NY, USA., Patel K; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Liao W; New York Genome Center, New York, NY, USA., Widman AJ; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Wong P; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Callahan MK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ha G; Division of Public Health Services, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Reed S; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Rotem D; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Frederick D; Division of Surgical Oncology, Massachussetts General Hospital, Boston, MA, USA., Sharova T; Division of Surgical Oncology, Massachussetts General Hospital, Boston, MA, USA., Miao B; Division of Surgical Oncology, Massachussetts General Hospital, Boston, MA, USA., Kim T; Division of Surgical Oncology, Massachussetts General Hospital, Boston, MA, USA., Gydush G; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Rhoades J; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Huang KY; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Omans ND; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Bolan PO; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Lipsky AH; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Ang C; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Malbari M; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Spinelli CF; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Kazancioglu S; New York Genome Center, New York, NY, USA., Runnels AM; New York Genome Center, New York, NY, USA., Fennessey S; New York Genome Center, New York, NY, USA., Stolte C; New York Genome Center, New York, NY, USA., Gaiti F; New York Genome Center, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Inghirami GG; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Adalsteinsson V; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Houck-Loomis B; New York Genome Center, New York, NY, USA., Ishii J; New York Genome Center, New York, NY, USA., Wolchok JD; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Boland G; Division of Surgical Oncology, Massachussetts General Hospital, Boston, MA, USA., Robine N; New York Genome Center, New York, NY, USA., Altorki NK; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA., Landau DA; New York Genome Center, New York, NY, USA. dlandau@nygenome.org.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. dlandau@nygenome.org.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2020 Jul; Vol. 26 (7), pp. 1114-1124. Date of Electronic Publication: 2020 Jun 01.
DOI: 10.1038/s41591-020-0915-3
Abstrakt: 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.
Databáze: MEDLINE
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