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Objective To analyze the consistency of plasma circulating tumor DNA (ctDNA) and tumor tissue DNA in detecting KRAS/NRAS/BRAF/PIK3CA gene mutations in patients with advanced colorectal cancer, and to explore the factors affecting the consistency. Methods Patients with advanced colorectal cancer who were treated in Zhongshan Hospital Fudan University from December 2018 to May 2020 were enrolled. The results of plasma and tissue gene detection, clinicopathological information and treatment were collected. The consistency and influencing fac