Abstract
To assess the impact of somatic gene mutations on survival among patients undergoing resection of colorectal liver metastases (CLM).Background:Patients undergoing CLM resection have heterogeneous outcomes, and accurate risk stratification is necessary to optimize patient selection for surgery.Methods:Next-generation sequencing of 50 cancer-related genes was performed from primary tumors and/or liver metastases in 401 patients undergoing CLM resection. Missense TP53 mutations were classified by the evolutionary action score (EAp53) - a novel approach that dichotomizes mutations as low or high risk.Results:The most frequent somatic gene mutations were TP53 (65.6%), followed by KRAS (48.1%) and APC (47.4%). Double mutation in RAS/TP53, identified in 31.4% of patients, was correlated with primary tumor location in the right colon (P = 0.006). On multivariable analysis, RAS/TP53 double mutation was an independent predictor of shorter overall survival (hazard ratio 2.62, 95% confidence interval 1.41-4.87, P = 0.002). In patients with co-mutated RAS, EAp53 high-risk mutations were associated with shorter 5-year overall survival of 12.2%, compared with 55.7% for TP53 wild type (P < 0.001). The negative prognostic effects of RAS and TP53 mutations were limited to tumors harboring mutations in both genes.Conclusions:Concomitant RAS and TP53 mutations are associated with decreased survival after CLM resection. A high EAp53 predicts a subset of patients with worse prognosis. These preliminary analyses suggest that surgical resection of liver metastases should be carefully considered in this subset of patients.
Original language | English (US) |
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Pages (from-to) | 917-923 |
Number of pages | 7 |
Journal | Annals of surgery |
Volume | 269 |
Issue number | 5 |
DOIs | |
State | Published - May 1 2019 |
Keywords
- RAS
- TP53
- colorectal liver metastases
ASJC Scopus subject areas
- Surgery
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