Double KRAS and BRAF Mutations in Surgically Treated Colorectal Cancer Liver Metastases: An International, Multi-institutional Case Series ANTICANCER RESEARCH Deshwar, A., Margonis, G., Andreatos, N., Barbon, C., Wang, J., Buettner, S., Wagner, D., Sasaki, K., Beer, A., Loes, I., Pikoulis, E., Damaskos, C., Garmpis, N., Kamphues, K., He, J., Kaczirek, K., Poultsides, G., Lonning, P., Mischinger, H., Aucejo, F. N., Kreis, M. E., Wolfgang, C. L., Weis, M. J. 2018; 38 (5): 2891–95


While previously believed to be mutually exclusive, concomitant mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS)- and V-raf murine sarcoma b-viral oncogene homolog B1 (BRAF)-mutated colorectal carcinoma (CRC), has been described in rare instances and been associated with advanced-stage disease. The present case series is the first to report on the implications of concurrent KRAS/BRAF mutations among surgically treated patients, and the largest set of patients with surgically treated colorectal liver metastasis (CRLM) and data on KRAS/BRAF mutational status thus far described.We present cases from an international, multi-institutional cohort of patients that underwent hepatic resection for CRLM between 2000-2015 at seven tertiary centers. The incidence of KRAS/BRAF mutation in patients with CRLM was 0.5% (4/820). Of these cases, patient 1 (T2N1 primary, G13D/V600E), patient 2 (T3N1 primary, G12V/V600E) and patient 3 (T4N2 primary, G13D/D594N) succumbed to their disease within 485, 236 and 79 days respectively, post-hepatic resection. Patient 4 (T4 primary, G12S/G469S) was alive 416 days after hepatic resection.The present case series suggests that the incidence of concomitant KRAS/BRAF mutations in surgical cohorts may be higher than previously hypothesized, and associated with more variable survival outcomes than expected.

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