Multifocal Clonal Evolution Characterized Using Circulating Tumor DNA Compared with Tumor Biopsies in Metastatic Colorectal Cancer by Targeted Next Generation Sequencing

OBJECTIVE: Intratumor clonal heterogeneity limits efficacy and duration of response to targeted treatments in metastatic cancer. About 50% of colorectal cancer patients have such distant metastases, accounting for virtually all deaths from the disease. We followed a patient with metastatic colon carcinoma who had undergone several surgeries after being diagnosed with colorectal cancer in 2006 and had survived for over 10 years. STUDY DESIGN: We characterized 5 tumor biopsies and 1 plasma sample collected at clinical follow-up using high throughput sequencing. RESULTS: Serial changes in circulating levels of subclonal private mutations correlated with different treatment responses between metastatic sites. CONCLUSION: This comparison of biopsy and plasma sample in a single patient with metastatic colorectal cancer shows that circulating tumor DNA can allow real-time sampling of multifocal clonal evolution. Through our research, we hope the information of the mutations in this patient would assist studying the relationship between mutations and survival.