Correlation of oncogenic mutations in circulating cell-free DNA (cfDNA) and tumor tissue through a multiplex sequencing platform in patients under consideration for phase I trials

6 Background: Previous studies suggest that tumoral cfDNA is a potential biomarker in cancer. Methods: Prospective collection of samples from patients (pts) referred to a phase I trials unit, in 2 cohorts: “A”(manual isolation of cfDNA, Sep09-Dec10) and “B”(robotic isolation, Jan11-Sep11) and from 41 healthy volunteers (HV). CfDNA and tumor DNA from matched formalin-fixed paraffin-embedded (FFPE) tissue were isolated, quantified and analyzed for 238 oncogenic mutations (OM) in 19 oncogenes using Sequenom OncoCarta Panel 1.0. Mutation data were used for trial allocation when available. Statistical analyses used Pearson’s Chi-squared test and Mann-Whitney test. Results: 280 pts were included: breast (60; 21%), ovarian (44; 16%), and colorectal (42; 15%). 265 (95%) plasma and 194 (69%) FFPE samples were suitable for analysis. In 181 pts (65%) both samples were available for comparison. Median turnover time for cfDNA 7 days (range 5-14). Median [cfDNA] (concentration; ng/ml) in pts was higher than in HV (“A” 21 v 6.4;p