High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants.

Autor: Razavi P; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. razavip@mskcc.org.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. razavip@mskcc.org., Li BT; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Brown DN; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Jung B; GRAIL, Inc., Menlo Park, CA, USA., Hubbell E; GRAIL, Inc., Menlo Park, CA, USA., Shen R; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Abida W; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Juluru K; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., De Bruijn I; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hou C; GRAIL, Inc., Menlo Park, CA, USA., Venn O; GRAIL, Inc., Menlo Park, CA, USA., Lim R; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Anand A; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Maddala T; GRAIL, Inc., Menlo Park, CA, USA., Gnerre S; GRAIL, Inc., Menlo Park, CA, USA., Vijaya Satya R; GRAIL, Inc., Menlo Park, CA, USA., Liu Q; GRAIL, Inc., Menlo Park, CA, USA., Shen L; GRAIL, Inc., Menlo Park, CA, USA., Eattock N; GRAIL, Inc., Menlo Park, CA, USA., Yue J; GRAIL, Inc., Menlo Park, CA, USA., Blocker AW; GRAIL, Inc., Menlo Park, CA, USA.; Foresite Capital Management, San Francisco, CA, USA., Lee M; GRAIL, Inc., Menlo Park, CA, USA.; Genentech, San Francisco, CA, USA., Sehnert A; GRAIL, Inc., Menlo Park, CA, USA.; MyoKardia, San Francisco, CA, USA., Xu H; GRAIL, Inc., Menlo Park, CA, USA., Hall MP; GRAIL, Inc., Menlo Park, CA, USA., Santiago-Zayas A; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Novotny WF; GRAIL, Inc., Menlo Park, CA, USA.; BeiGene, San Mateo, CA, USA., Isbell JM; Department of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Rusch VW; Department of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Plitas G; Department of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Heerdt AS; Department of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Ladanyi M; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hyman DM; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Jones DR; Department of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Morrow M; Department of Surgery, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Riely GJ; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Scher HI; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Rudin CM; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Robson ME; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Diaz LA Jr; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA., Solit DB; Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Aravanis AM; GRAIL, Inc., Menlo Park, CA, USA., Reis-Filho JS; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. reisfilj@mskcc.org.; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. reisfilj@mskcc.org.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2019 Dec; Vol. 25 (12), pp. 1928-1937. Date of Electronic Publication: 2019 Nov 25.
DOI: 10.1038/s41591-019-0652-7
Abstrakt: Accurate identification of tumor-derived somatic variants in plasma circulating cell-free DNA (cfDNA) requires understanding of the various biological compartments contributing to the cfDNA pool. We sought to define the technical feasibility of a high-intensity sequencing assay of cfDNA and matched white blood cell DNA covering a large genomic region (508 genes; 2 megabases; >60,000× raw depth) in a prospective study of 124 patients with metastatic cancer, with contemporaneous matched tumor tissue biopsies, and 47 controls without cancer. The assay displayed high sensitivity and specificity, allowing for de novo detection of tumor-derived mutations and inference of tumor mutational burden, microsatellite instability, mutational signatures and sources of somatic mutations identified in cfDNA. The vast majority of cfDNA mutations (81.6% in controls and 53.2% in patients with cancer) had features consistent with clonal hematopoiesis. This cfDNA sequencing approach revealed that clonal hematopoiesis constitutes a pervasive biological phenomenon, emphasizing the importance of matched cfDNA-white blood cell sequencing for accurate variant interpretation.
Databáze: MEDLINE
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