典型文献
Comprehensive characterization of CRC with germline mutations reveals a distinct somatic mutational landscape and elevated cancer risk in the Chinese population
文献摘要：
Objective: Hereditary colorectal cancer (CRC) accounts for approximately 5％–10％ of all CRC cases. The full profile of CRC-related germline mutations and the corresponding somatic mutational profile have not been fully determined in the Chinese population. Methods: We performed the first population study investigating the germline mutation status in more than 1,000 (n = 1,923) Chinese patients with CRC and examined their relationship with the somatic mutational landscape. Germline alterations were examined with a 58-gene next-generation sequencing panel, and somatic alterations were examined with a 605-gene panel. Results: A total of 92 pathogenic (P) mutations were identified in 85 patients, and 81 likely pathogenic (LP) germline mutations were identified in 62 patients, accounting for 7.6％ (147/1,923) of all patients. MSH2 and APC was the most mutated gene in the Lynch syndrome and non-Lynch syndrome groups, respectively. Patients with P/LP mutations had a significantly higher ratio of microsatellite instability, highly deficient mismatch repair, family history of CRC, and lower age. The somatic mutational landscape revealed a significantly higher mutational frequency in the P group and a trend toward higher copy number variations in the non-P group. The Lynch syndrome group had a significantly higher mutational frequency and tumor mutational burden than the non-Lynch syndrome group. Clustering analysis revealed that the Notch signaling pathway was uniquely clustered in the Lynch syndrome group, and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group. Population risk analysis indicated that the overall odds ratio was 11.13 (95％ CI: 8.289–15.44) for the P group and 20.68 (95％ CI: 12.89–33.18) for the LP group. Conclusions: Distinct features were revealed in Chinese patients with CRC with germline mutations. The Notch signaling pathway was uniquely clustered in the Lynch syndrome group, and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group. Patients with P/LP germline mutations exhibited higher CRC risk.
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作者姓名：
Jianfei Yao;Yunhuan Zhen;Jing Fan;Yuan Gong;Yumeng Ye;Shaohua Guo;Hongyi Liu;Xiaoyun Li;Guosheng Li;Pan Yang;Xiaohui Wang;Danni Liu;Tanxiao Huang;Huiya Cao;Peisu Suo;Yuemin Li;Jingbo Yu;Lele Song
作者机构：
Department of Radiotherapy,the Eighth Medical Center of the Chinese PLA General Hospital,Beijing 100091,China;HaploX Biotechnology,Shenzhen 518057,China;Department of Colorectal Surgery,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China;International Business School,Beijing Foreign Studies University,Beijing 100089,China;Department of Gastroenterology,the Second Medical Center of the Chinese PLA General Hospital,Beijing 100853,China;Department of Experimental Pathology,Beijing Institute of Radiation Medicine,Beijing 100850,China;Department of General Surgery,the First Medical Center of the Chinese PLA General Hospital,Beijing 100853,China;Department of Hepatobiliary Surgery,Dalian Municipal Central Hospital,Dalian Medical University,Dalian 116033,China;Comprehensive Liver Cancer Department,the Fifth Medical Center of the Chinese PLA General Hospital,Beijing 100039,China
文献出处：
引用格式：
[1]Jianfei Yao;Yunhuan Zhen;Jing Fan;Yuan Gong;Yumeng Ye;Shaohua Guo;Hongyi Liu;Xiaoyun Li;Guosheng Li;Pan Yang;Xiaohui Wang;Danni Liu;Tanxiao Huang;Huiya Cao;Peisu Suo;Yuemin Li;Jingbo Yu;Lele Song-.Comprehensive characterization of CRC with germline mutations reveals a distinct somatic mutational landscape and elevated cancer risk in the Chinese population)[J].癌症生物学与医学（英文版）,2022(05):707-732
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0.39708
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