ABSTRACT
Objective: To explore the significance of next-generation sequencing for the screening of high-risk hereditary gastrointesti-nal cancer patients and the value of high-risk factors in screening. Methods: Twenty-five hereditary high-risk gastrointestinal cancer pa-tients from March 2016 to April 2016 in Peking University Cancer Hospital were enrolled. They received detection of 42 hereditary can-cer syndrome related genes by next-generation sequencing. Results: Out of 25 patients enrolled, 24% (6/25) patients had pathological germline mutations. The expression of mismatch repair protein was absent in 50% (3/6) patients. There were 83% (5/6) patients with family history of malignant tumors and were diagnosed when younger than 50 years. Six patients had hereditary cancer syndrome re-lated gene mutation, 1 patient had MYH gene missense mutation, 1 patient had APC gene deletion mutation, 4 patients had heredi-tary colorectal cancer related gene mutation, including MLH1, MLH3, and TGFBR2 germline missense mutations as well as MSH6 non-sense mutation. Conclusions: Out of 25 patients with high-risk factors of hereditary gastrointestinal cancer, 6 (24%) had pathological germline mutations. Given the high frequency and wide spectrum of mutations, the application of next-generation sequencing for screening of hereditary high-risk gastrointestinal cancer patients has the clinical value for improving the positive rate of diagnosis.