Comparative Analysis of Primary and Metastatic Colorectal Cancer

Molecular profiling for somatic mutations that predict response to anti-EGFR therapy in colorectal cancer (CRC) has become standard practice. However, abundant tissue from metastatic lesions is not always available from patients with metastatic CRC. Concerns involving genetic heterogeneity between primary and metastatic lesions have called into question the suitability of profiling primary tumors in patients with metastatic disease. Further, the identification of discordant mutations between matched primary and metastatic tumors would be of biological interest for the delineation of biomarkers of tumor progression and metastasis. To explore the degree of genetic heterogeneity between matched primary and metastatic tumors in CRC, we performed whole genome sequencing of four patient "trios" comprised of a primary colon tumor, a liver metastasis, and matched normal (non-cancerous) tissue. Somatic mutations and indels were called in each tumor and compared between primary and metastatic lesions.]]> Patients with metastatic colorectal cancer were included if they consented to a tissue acquisition protocol approved by the Memorial Sloan Kettering Cancer Center IRB and if sufficient material for whole genome sequencing was available from a primary tumor, metastatic tumor, and matched normal tissue.]]>