典型文献
Lynch syndrome pre-screening and comprehensive characterization in a multi-center large cohort of Chinese patients with colorectal cancer
文献摘要：
Objective: Lynch syndrome (LS) pre-screening methods remain under-investigated in colorectal cancers (CRCs) in Asia. Here, we aimed to systematically investigate LS pre-screening and comprehensively characterize LS CRCs. Methods: Microsatellite instability (MSI) and germline variants of DNA mismatch repair (MMR) genes were examined in 406 deficient MMR (dMMR) and 250 proficient MMR CRCs. The genetic differences between LS and sporadic CRCs were studied with whole exome sequencing analysis. Results: The incidence of dMMR in Chinese patients with CRCs was 13.8％. Consistency analysis between MMR immunohistochemistry (IHC) and MSI testing showed the kappa value was 0.758. With next-generation sequencing (NGS), germline variants were detected in 154 CRCs. Finally, 88 patients with CRC were identified as having LS by Sanger sequencing. Among them, we discovered 21 previously unreported pathogenic germline variants of MMR genes. Chinese patients with LS, compared with sporadic CRCs, tended to be early-onset, right-sided, early-stage and mucinous. Overall, the performance of MMR IHC and MSI testing for LS pre-screening was comparable: the area under the ROC curve for dMMR, MSI-H, and MSI-H/L was 0.725, 0.750, and 0.745, respectively. dMMR_MSI-H LS and sporadic CRCs showed substantial differences in somatic genetic characteristics, including different variant frequencies of APC, CREBBP, and KRAS, as well as different enriched pathways of VEGF, Notch, TGFβR, mTOR, ErbB, and Rac protein signal transduction. Conclusions: MMR IHC and MSI testing were effective methods for LS pre-screening. The revealed clinical and somatic genetic characteristics in LS CRCs may have the potential to improve the performance of LS pre-screening in combination with dMMR/MSI.
文献关键词：
中图分类号：
作者姓名：
Yan Li;Lihong Fan;Jianming Zheng;Xiu Nie;Yu Sun;Qin Feng;Shenyi Lian;Wenqi Bai;Weijing Cai;Yanan Yang;Bo Su;Yanfeng Xi;Dongmei Lin
作者机构：
Department of Pathology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Department of Respiration Medicine,Shanghai Tenth People's Hospital,School of Medicine,Tongji University,Shanghai 200072,China;Department of Pathology,Changhai Hospital of Shanghai,Shanghai 200433,China;Department of Pathology,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Peking University Cancer Hospital&Institute,Beijing 100142,China;Department of Colorectal Surgery,Shanxi Cancer Hospital,Taiyuan 030013,China;Shanghai Tongshu Biotechnology Co.,Ltd,Shanghai 200120,China;Department of Biochemistry and Molecular Biology,Mayo Clinic,Rochester,MN 55905,USA;Central Laboratory,Shanghai Pulmonary Hospital,School of Medicine,Tongji University,Shanghai 200433,China;Department of Pathology,Shanxi Cancer Hospital,Taiyuan 030013,China
文献出处：
引用格式：
[1]Yan Li;Lihong Fan;Jianming Zheng;Xiu Nie;Yu Sun;Qin Feng;Shenyi Lian;Wenqi Bai;Weijing Cai;Yanan Yang;Bo Su;Yanfeng Xi;Dongmei Lin-.Lynch syndrome pre-screening and comprehensive characterization in a multi-center large cohort of Chinese patients with colorectal cancer)[J].癌症生物学与医学（英文版）,2022(08):1235-1248
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B类：
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AB值：
0.484556
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