• Mingyang Li, Xingjian Yan, He Liu, Wenhao Miao, Wenbo Wu, Yuyang Zhao, Chungang Wang, and Haitao Liu.
• Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China.
• Transl Res. 2024 Mar 1; 265: 263526-35.

AbstractLynch syndrome, an autosomal dominant hereditary disease arising from mutations in mismatch repair genes, is linked to the development of multiple tumor types, notably colorectal cancer, endometrial carcinoma and upper urinary tract urothelial carcinoma. In this study, we present the case of a young patient diagnosed with upper urinary tract urothelial carcinoma, notable for a familial history of diverse malignancies. By employing genetic analysis, we verified the presence of Lynch syndrome within the family and detected novel variants, MSH2 p.A604D and TSC2 p.C738Y, utilizing NGS technology. Subsequently, we conducted validation experiments to assess the pathogenicity of the MSH2 and TSC2 variants. We illustrated that the MSH2 variant can result in diminished MSH2 expression, compromised mismatch repair function, and induce resistance to cisplatin in urothelial carcinoma. Furthermore, we substantiated the promotional impact of the identified TSC2 variant on urothelial carcinoma, encompassing proliferation, invasion, and migration. Significantly, we found that the MSH2 p.A604D variant and TSC2 p.C738Y variant synergistically enhance the promotion of urothelial carcinoma.Copyright © 2023. Published by Elsevier Inc.

19 keywords...

hide…