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Comprehensive genomic sequencing (CGS) enables us to detect numerous genetic alterations in a single assay. We aimed to identify molecular markers for predicting prognosis and conversion surgery in Stage IV colorectal cancer (CRC) using CGS. One-hundred eleven patients with Stage IV CRC who underwent primary tumor resection were analyzed. We retrospectively investigated genetic alterations using CGS of a 415-gene panel. Clinicopathological variables and genetic alterations were analyzed to identify independent prognostic factors of overall survival (OS). Forty-five of 111 patients had R0 resection; of these, 11 patients underwent conversion surgery. Univariate and multivariate analyses identified histopathological grade 3, R0 resection,  BRAF  V600E mutation, and  SRC  mutation as independent prognostic factors for OS ( P  = 0.041,  P  = 0.013,  P  = 0.005, and  P  = 0.023, respectively).  BRAF  V600E and  SRC  mutations were mutually exclusive, and  SRC  mutation was significantly associated with left-sided tumor and liver metastasis compared to  BRAF  V600E mutation ( P  = 0.016 and  P  = 0.025, respectively). Eleven of the 74 initially unresectable patients underwent conversion surgery for R0 resection, yet none harbored  BRAF  V600E or  SRC  mutations.  BRAF  V600E and  SRC  mutations are important molecular markers which can predict prognosis and conversion surgery in Stage IV CRC.

BRAF V600E and SRC mutations as molecular markers for predicting prognosis and conversion surgery in Stage IV colorectal cancer