Inherited mutations in Chinese patients with upper tract urothelial carcinoma

作者：Junlong Wu, Shengming Jin, Chengyuan Gu, Wei Yu, Yao Zhu, Andrea Necchi, Shahrokh F. Shariat, Jian Pan, Hualei Gan, Bo Dai, Hailiang Zhang, Guohai Shi, Yu Zhu, Yijun Shen, Yiping Zhu, Dingwei Ye · 发表于：Cell Reports Medicine · 年份：2023 · DOI：10.1016/j.xcrm.2022.100883 · 被引用次数：8 · 研究领域：Bladder and Urothelial Cancer Treatments、Genetic factors in colorectal cancer、Viral-associated cancers and disorders

Upper tract urothelial carcinoma (UTUC) accounts for 10% of urothelial carcinomas (UCs) and has a substantial hereditary component. However, the majority of our knowledge of germline spectrum comes from bladder cancer (BCa) data in White populations. Here, we sequence 309 Chinese UTUC cases and identify 71 germline pathogenic/likely pathogenic (P/LP) mutations in 62 patients (20.1%). Compared with White cases, we observe disparities and similarities in inherited mutational profiles. Association analysis reveals that germline P/LP mutations in MSH2, BRCA2, BRCA1, and BRIP1 significantly increase UTUC risk in Chinese populations. Furthermore, germline P/LP mutation in homologous recombination genes indicates poor prognosis for non-metastatic UTUC. Finally, we perform paired sequencing and observe significant correlations between germline mutation patterns and tumor subtypes. This study highlights the importance of genetic testing in patients with UTUC and calls for germline data from various ethnicities to better understand this disease.