Copy number analysis of liver metastases from colorectal cancer

Almost half of all patients diagnosed with colorectal cancer develop liver metastases. The potential role of intra-individual metastatic heterogeneity remains poorly characterized. By high-resolution DNA copy number analyses and a novel approach based on pair-wise genetic distance, we examined the genetic heterogeneity among multiple liver metastatic deposits obtained from 45 patients subject to curative liver resection. We found large variation in intra-individual metastatic heterogeneity. A high level of heterogeneity was associated with poor patient survival. Patients with metachronous metastases who received chemotherapy had significantly more heterogeneity than chemonaïve patients. Genome-wide copy number analysis was performed on fresh frozen tissue samples from 134 liver metastatic deposits and 6 primary tumors from 45 patients with metastatic colorectal cancer using the Affymetrix SNP 6.0 Array