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Individualised multiplexed circulating tumour DNA assays for monitoring of tumour presence in patients after colorectal cancer surgery. (Sci Rep, Jan 2017)

Ng SB1, Chua C2, Ng M2, Gan A3, Poon PS1, Teo M4, Fu C5, Leow WQ6, Lim KH6, Chung A7, Koo SL2, Choo SP2, Ho D2, Rozen S8, Tan P8,9, Wong M5, Burkholder WF1, Tan IB2,3,8.

1 Microfluidics Systems Biology, Institute of Molecular and Cell Biology, Singapore.
2 Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
3 Genome Institute of Singapore, Singapore.
4 Division of Surgical Oncology, National Cancer Centre Singapore, Singapore.
5 Department of Colorectal Surgery, Singapore General Hospital, Singapore.
6 Department of Pathology Anatomical Pathology, Singapore General Hospital, Singapore.
7 Department of Hepatopancreatobiliary/Transplant Surgery, Singapore General Hospital, Singapore.
8 Cancer & Stem Cell Biology Program, Duke-NUS Medical School, Singapore.
9 Cancer Science Institute, National University of Singapore, Singapore.

Abstract
Circulating tumour DNA (ctDNA) has the potential to be a specific biomarker for the monitoring of tumours in patients with colorectal cancer (CRC). Here, our aim was to develop a personalised surveillance strategy to monitor the clinical course of CRC after surgery. We developed patient-specific ctDNA assays based on multiplexed detection of somatic mutations identified from patient primary tumours, and applied them to detect ctDNA in 44 CRC patients, analysing a total of 260 plasma samples. We found that ctDNA detection correlated with clinical events – it is detectable in pre-operative but not post-operative plasma, and also in patients with recurrent CRC. We also detected ctDNA in 11 out of 15 cases at or before clinical or radiological recurrence of CRC, indicating the potential of our assay for early detection of metastasis. We further present data from a patient with multiple primary cancers to demonstrate the specificity of our assays to distinguish between CRC recurrence and a second primary cancer. Our approach can complement current methods for surveillance of CRC by adding an individualised biological component, allowing us not only to point to the presence of residual or recurrent disease, but also attribute it to the original cancer.

PMID: 28102343