TY - JOUR
T1 - White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer
AU - Leal, Alessandro
AU - van Grieken, Nicole C.T.
AU - Palsgrove, Doreen N.
AU - Phallen, Jillian
AU - Medina, Jamie E.
AU - Hruban, Carolyn
AU - Broeckaert, Mark A.M.
AU - Anagnostou, Valsamo
AU - Adleff, Vilmos
AU - Bruhm, Daniel C.
AU - Canzoniero, Jenna V.
AU - Fiksel, Jacob
AU - Nordsmark, Marianne
AU - Warmerdam, Fabienne A.R.M.
AU - Verheul, Henk M.W.
AU - van Spronsen, Dick Johan
AU - Beerepoot, Laurens V.
AU - Geenen, Maud M.
AU - Portielje, Johanneke E.A.
AU - Jansen, Edwin P.M.
AU - van Sandick, Johanna
AU - Meershoek-Klein Kranenbarg, Elma
AU - van Laarhoven, Hanneke W.M.
AU - van der Peet, Donald L.
AU - van de Velde, Cornelis J.H.
AU - Verheij, Marcel
AU - Fijneman, Remond
AU - Scharpf, Robert B.
AU - Meijer, Gerrit A.
AU - Cats, Annemieke
AU - Velculescu, Victor E.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Liquid 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.
AB - Liquid 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.
UR - http://www.scopus.com/inward/record.url?scp=85078362335&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-020-14310-3
DO - https://doi.org/10.1038/s41467-020-14310-3
M3 - Article
C2 - 31988276
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 525
ER -