TY - JOUR
T1 - Direct detection of early-stage cancers using circulating tumor DNA
AU - Phallen, Jillian
AU - Sausen, Mark
AU - Adleff, Vilmos
AU - Leal, Alessandro
AU - Hruban, Carolyn
AU - White, James
AU - Anagnostou, Valsamo
AU - Fiksel, Jacob
AU - Cristiano, Stephen
AU - Papp, Eniko
AU - Speir, Savannah
AU - Reinert, Thomas
AU - Orntoft, Mai Britt Worm
AU - Woodward, Brian D.
AU - Murphy, Derek
AU - Parpart-Li, Sonya
AU - Riley, David
AU - Nesselbush, Monica
AU - Sengamalay, Naomi
AU - Georgiadis, Andrew
AU - Li, Qing Kay
AU - Madsen, Mogens Rørbæk
AU - Mortensen, Frank Viborg
AU - Huiskens, Joost
AU - Punt, Cornelis
AU - Van Grieken, Nicole
AU - Fijneman, Remond
AU - Meijer, Gerrit
AU - Husain, Hatim
AU - Scharpf, Robert B.
AU - Diaz, Luis A.
AU - Jones, Sin
AU - Angiuoli, Sam
AU - Ørntoft, Torben
AU - Nielsen, Hans Jørgen
AU - Andersen, Claus Lindbjerg
AU - Velculescu, Victor E.
PY - 2017/8/16
Y1 - 2017/8/16
N2 - Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.
AB - Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.
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U2 - 10.1126/scitranslmed.aan2415
DO - 10.1126/scitranslmed.aan2415
M3 - Article
C2 - 28814544
AN - SCOPUS:85027717075
SN - 1946-6234
VL - 9
JO - Science translational medicine
JF - Science translational medicine
IS - 403
M1 - eaan2415
ER -