Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring Journal Article
| Authors: | Zviran, A.; Schulman, R. C.; Shah, M.; Hill, S. T. K.; Deochand, S.; Khamnei, C. C.; Maloney, D.; Patel, K.; Liao, W.; Widman, A. J.; Wong, P.; Callahan, M. K.; Ha, G.; Reed, S.; Rotem, D.; Frederick, D.; Sharova, T.; Miao, B.; Kim, T.; Gydush, G.; Rhoades, J.; Huang, K. Y.; Omans, N. D.; Bolan, P. O.; Lipsky, A. H.; Ang, C.; Malbari, M.; Spinelli, C. F.; Kazancioglu, S.; Runnels, A. M.; Fennessey, S.; Stolte, C.; Gaiti, F.; Inghirami, G. G.; Adalsteinsson, V.; Houck-Loomis, B.; Ishii, J.; Wolchok, J. D.; Boland, G.; Robine, N.; Altorki, N. K.; Landau, D. A. |
| Article Title: | Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring |
| 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. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | adult; clinical article; controlled study; unclassified drug; human cell; somatic mutation; postoperative period; sensitivity and specificity; tumor volume; cohort analysis; genome analysis; adverse outcome; dna; minimal residual disease; cancer epidemiology; dna mutational analysis; human; male; female; priority journal; article; whole genome sequencing; cell free dna; solid malignant neoplasm |
| Journal Title: | Nature Medicine |
| Volume: | 26 |
| Issue: | 7 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-07-01 |
| Start Page: | 1114 |
| End Page: | 1124 |
| Language: | English |
| DOI: | 10.1038/s41591-020-0915-3 |
| PUBMED: | 32483360 |
| PROVIDER: | scopus |
| PMCID: | PMC8108131 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 August 2020 -- Source: Scopus |
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