title: Individualised multiplexed circulating tumour DNA assays for monitoring of tumour presence in patients after colorectal cancer surgery.
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.
authors.affiliation: Microfluidics Systems Biology, Institute of Molecular and Cell Biology, Singapore.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Ng
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Clarinda
authors.initials: C
authors.lastname: Chua
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ng
authors.affiliation: Genome Institute of Singapore, Singapore.
authors.forename: Anna
authors.initials: A
authors.lastname: Gan
authors.affiliation: Microfluidics Systems Biology, Institute of Molecular and Cell Biology, Singapore.
authors.forename: Polly Sy
authors.initials: PS
authors.lastname: Poon
authors.affiliation: Division of Surgical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Melissa
authors.initials: M
authors.lastname: Teo
authors.affiliation: Department of Colorectal Surgery, Singapore General Hospital, Singapore.
authors.forename: Cherylin
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Pathology Anatomical Pathology, Singapore General Hospital, Singapore.
authors.forename: Wei Qiang
authors.initials: WQ
authors.lastname: Leow
authors.affiliation: Department of Pathology Anatomical Pathology, Singapore General Hospital, Singapore.
authors.forename: Kiat Hon
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Department of Hepatopancreatobiliary/Transplant Surgery, Singapore General Hospital, Singapore.
authors.forename: Alexander
authors.initials: A
authors.lastname: Chung
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Si-Lin
authors.initials: SL
authors.lastname: Koo
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Su Pin
authors.initials: SP
authors.lastname: Choo
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Danliang
authors.initials: D
authors.lastname: Ho
authors.affiliation: Cancer &Stem Cell Biology Program, Duke-NUS Medical School, Singapore.
authors.forename: Steve
authors.initials: S
authors.lastname: Rozen
authors.affiliation: Cancer &Stem Cell Biology Program, Duke-NUS Medical School, Singapore.|Cancer Science Institute, National University of Singapore, Singapore.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Colorectal Surgery, Singapore General Hospital, Singapore.
authors.forename: Mark
authors.initials: M
authors.lastname: Wong
authors.affiliation: Microfluidics Systems Biology, Institute of Molecular and Cell Biology, Singapore.
authors.forename: William F
authors.initials: WF
authors.lastname: Burkholder
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore.|Genome Institute of Singapore, Singapore.|Cancer &Stem Cell Biology Program, Duke-NUS Medical School, Singapore.
authors.forename: Iain Beehuat
authors.initials: IB
authors.lastname: Tan
mesh_terms: D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D004273:DNA, Neoplasm; D006801:Humans; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D011184:Postoperative Period; D012008:Recurrence; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D057188:Workflow
chemical_list: D014408:Biomarkers, Tumor; D000074141:Circulating Tumor DNA; D004273:DNA, Neoplasm