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Objective:  Targeted deep sequencing was used to characterize the mutational spectrum of  APC  in Chinese colorectal tumors in comparison to that in Caucasians from The Cancer Genome Atlas (TCGA) and to investigate whether  APC  mutations can predict overall survival in CRC patients receiving adjuvant chemotherapy. Methods:  A total of 315 Chinese CRC patients including 241 stage II/III patients receiving fluorouracil-based adjuvant chemotherapy were included in this study. Next generation sequencing was carried out to detect somatic mutations on all  APC  exons. The associations between  APC  mutations and overall survival were determined by the Cox proportional hazards model. Results:APC  was mutated in 221 of 315 colorectal tumors (70.2%). Chinese CRC had a much higher frequency of missense mutations (16.2% vs. 2.4%), but a lower frequency of nonsense (41.0% vs. 54.2%) and frameshift mutations (10.5% vs. 18.4%) than Caucasian CRC. Among stage II/III patients receiving fluorouracil-based adjuvant chemotherapy,  APC  mutations showed a significant association with worse survival (HR = 1.69; 95% CI, 1.10-2.62;  p  = .0179). Of the mutation types, frameshift mutations conferred the highest risk of death (HR = 2.88; 95% CI, 1.54-5.37;  p  =.0009). Among individual mutation sites, Arg232Ter, the most frequent mutation in Chinese CRC, exhibited the strongest negative impact on survival (HR = 2.65; 95% CI, 1.16-6.03;  p  =.0202). Conclusion:APC  overall mutation was an independent predictor for overall survival of stage II/III CRC patients receiving fluorouracil-based chemotherapy.

Targeted deep sequencing reveals APC mutations as predictors of overall survival in Chinese colorectal patients receiving adjuvant chemotherapy