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Sci Transl Med. 2017 Aug 16;9(403). pii: eaan2415. doi: 10.1126/scitranslmed.aan2415.

Direct detection of early-stage cancers using circulating tumor DNA.

Author information

1
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
2
Personal Genome Diagnostics, Baltimore, MD 21224, USA.
3
Department of Molecular Medicine, Aarhus University Hospital, DK-8200 Aarhus, Denmark.
4
Division of Hematology and Oncology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
5
Department of Surgery, Herning Regional Hospital, DK-7400 Herning, Denmark.
6
Department of Surgical Gastroenterology, Aarhus University Hospital, DK-8000 Aarhus, Denmark.
7
Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
8
Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
9
Department of Pathology, VU University Medical Center, Amsterdam 1081 HV, Netherlands.
10
Department of Pathology, Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands.
11
Department of Surgical Gastroenterology 360, Hvidovre Hospital, Hvidovre, Denmark.
12
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. velculescu@jhmi.edu.

Abstract

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.

PMID:
28814544
DOI:
10.1126/scitranslmed.aan2415
[Indexed for MEDLINE]

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