为了评估泌尿系统透明细胞癌（CCA）的分子特征，研究其致病途径和可能的可行靶点。我们回顾性收集了1999年1月至2016年12月间CCA患者的数据；这些数据由两名病理学家独立进行了审查。我们根据临床病理特征选择了5例泌尿系统CCA患者。我们利用全外显子测序（WES）和后续生物信息学分析对这5例患者进行了基因突变谱及可能的致病途径研究。 研究对象均为女性，中位年龄62岁。所有肿瘤位于尿道，并表现出侵袭性行为和疾病进展。WES揭示出多种基因改变，包括驱动基因突变（AMER1、ARID1A、CHD4、KMT2D、KRAS、PBRM1、PIK3R1）以及其他具有抑制肿瘤和致癌作用的重要基因突变（CSMD3、KEAP1、SMARCA4、CACNA1D）。我们认为染色质重塑途径、MAPK信号通路、PI3K/AKT/mTOR途径和Wnt/β-连聚蛋白途径是潜在的致病途径，可作为靶向治疗的候选方案。 我们的研究结果揭示了这种极为罕见、预后差的肿瘤的分子背景，并可以帮助改善治疗选择。

To evaluate the molecular features of clear cell adenocarcinoma (CCA) of the urinary tract and investigate its pathogenic pathways and possible actionable targets.We retrospectively collected the data of patients with CCA between January 1999 and December 2016; the data were independently reviewed by two pathologists. We selected five cases of urinary CCA, based on the clinicopathological features. We analyzed these five cases by whole-exome sequencing (WES) and subsequent bioinformatics analyses to determine the mutational spectrum and possible pathogenic pathways.All patients were female with a median age of 62 years. All tumors were located in the urethra and showed aggressive behavior with disease progression. WES revealed several genetic alterations, including driver gene mutations (AMER1, ARID1A, CHD4, KMT2D, KRAS, PBRM1, PIK3R1) and mutations in other important genes with tumor-suppressive and oncogenic roles (CSMD3, KEAP1, SMARCA4, CACNA1D). We suggest putative pathogenic pathways (chromatin remodeling pathway, MAPK signaling pathway, PI3K/AKT/mTOR pathway and Wnt/β-catenin pathway) as candidates for targeted therapies.Our findings shed light on the molecular background of this extremely rare tumor with poor prognosis and can help improve treatment options.