White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer
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Published:2020-01-27
Issue:1
Volume:11
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Leal AlessandroORCID, van Grieken Nicole C. T.ORCID, Palsgrove Doreen N., Phallen Jillian, Medina Jamie E.ORCID, Hruban Carolyn, Broeckaert Mark A. M., Anagnostou ValsamoORCID, Adleff Vilmos, Bruhm Daniel C.ORCID, Canzoniero Jenna V., Fiksel Jacob, Nordsmark Marianne, Warmerdam Fabienne A. R. M., Verheul Henk M. W., van Spronsen Dick JohanORCID, Beerepoot Laurens V.ORCID, Geenen Maud M., Portielje Johanneke E. A., Jansen Edwin P. M.ORCID, van Sandick Johanna, Meershoek-Klein Kranenbarg ElmaORCID, van Laarhoven Hanneke W. M., van der Peet Donald L., van de Velde Cornelis J. H., Verheij Marcel, Fijneman RemondORCID, Scharpf Robert B., Meijer Gerrit A., Cats Annemieke, Velculescu Victor E.ORCID
Abstract
AbstractLiquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.
Funder
U.S. Department of Health & Human Services | NIH | National Cancer Institute EIF | Stand Up To Cancer Dr. Miriam and Sheldon G. Adelson Medical Research Foundation Mark Foundation for Cancer Research
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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