Circulating tumor DNA as a highly specific diagnostic marker for colorectal cancer.

Abstract

e22126 Background: Circulating tumor DNA (ctDNA) from cancer patient plasma is a promising biomarker with applications in screening, treatment selection, therapy response monitoring, minimal residual disease detection, and surveillance. We investigate the value of ctDNA as a biomarker in colorectal cancer to augment clinical decision-making. Methods: We present a ctDNA detection assay simultaneously capable of single molecule sensitivity, specificity to 0.01%– 0.001% mutation abundance versus wild-type, and multiplexing over 100 mutations from a single plasma sample. The employs a proprietary target selection process that removes wild-type DNA prior to library construction to greatly reduce the error rate of DNA sequencing. Using this assay, we analysed plasma from three cohorts of individuals including normal controls (n=13), age-matched normal controls (n=17), and colorectal cancer patients (n=17) across all stages of disease whose blood was drawn prior to treatment or surgery, and whose diagnosis confirms the presence of a tumor. Tissue from the primary tumor biopsy was also collected and analysed with the OnTarget assay. Results: We find a high correlation between the tumor mutational profile and the plasma mutation profile even for early stage patients demonstrating high sensitivity (92% plasma-tissue concordance over all patients) and exceptional specificity (100%: no false positives in normal cohorts). Additionally, mutations deemed from clinical evidence to originate from distant metastatic sites are detected in the plasma, highlighting the promise of the liquid biopsy approach for application in clinical care. We present concordance, sensitivity, and specificity results from the colorectal cancer patient cohort and the cohort of healthy individuals. Conclusions: Initial assay results from 30 healthy individuals and 17 CRC patients indicate that OnTarget detection of ctDNA provides an exceptionally specific assay for the presence of colorectal tumors and may have utility as a biomarker to guide colorectal cancer management across early-stage and metastatic disease.