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Dynamic Monitoring of Driver Gene Mutation Profiles in Plasma Cfdna Using an 85 Gene Panel for Postoperative Prognosis in Colorectal Cancer.

JOURNAL OF CLINICAL ONCOLOGY(2018)

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摘要
e15536 Background: Postoperative monitoring of patients with colorectal cancer (CRC) requires sensitive biomarkers associated with response to therapy following surgery. Identifying molecular residual disease (MRD) using ctDNA after treatment of CRC could facilitate early intervention and precision adjuvant therapies. Methods: The present study enrolled 30 patients with CRC. All patients underwent surgery; and a number of patients underwent postoperative chemotherapy. Tumor tissues and serial blood samples were collected from each patient; and somatic mutations from each sample were identified using next-generation sequencing. Results: The mutational landscape and mutational dynamics were analyzed for each patient. These results were compared with changes in CEA levels. In 83% (25/30) of patients, at least 1 of the variants detected in tumor tissue was also detected in plasma. The majority of actionable mutations detected in tissue were also detected in plasma. A number of driver genes were selected, including TP53, APC, PIK3CA and KRAS, to monitor the postoperative outcome of the 30 CRC patients. Driver mutations were detected in the preoperative plasma of 25 patients; and marked decreases in postoperative plasma mutation levels compared to preoperative levels were observed. In 5 patients, driver mutations were not detected in either preoperative or postoperative plasma. In the 2 patients with metastatic CRC, the ctDNA level increased significantly; however no marked changes in CEA level were observed. Conclusions: The results of ctDNA analysis correlate well with the presence or absence of tumors in preoperative and postoperative patients with CRC; and shows promise for identifying residual/recurrent disease earlier. In summary, ctDNA analysis is a highly sensitive and specific method for predicting postoperative outcome in patients with CRC.
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