Wen Lexiaochuan, Britton Cameron J, Garje Rohan, Darbro Benjamin W, Packiam Vignesh T
Department of Urology, Mayo Clinic, Rochester, MN, USA.
Division of Hematology, Oncology, Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
Asian J Urol. 2021 Oct;8(4):391-399. doi: 10.1016/j.ajur.2021.06.005. Epub 2021 Jun 26.
The development of rapid genome sequencing has greatly enhanced our understanding of the molecular biology underlying many malignancies. Whole exome sequencing has highlighted the individualistic nature of malignancies on a patient-to-patient basis and begun to revolutionize therapeutic approaches. In recent years, whole genome sequencing of urothelial malignancies has identified a host of somatic mutations which contribute to growth, progression, and metastasis of urothelial carcinoma of the bladder and upper tract urothelial carcinoma. As genetic sequencing continues, additional targets will be identified, allowing development of novel therapeutic agents targeting cancer on a molecular level, with the goal of delivering highly individualized care based on the underlying mutational profile of the patient's malignancy. In this review, we aim to discuss known genetic alterations of urothelial malignancy and the implications these mutations carry in terms of prognostication and development of targeted therapeutic agents. We will focus on RNA-expression profiling and genomic DNA profiling, with a focus on comprehensive whole exome and whole genome sequencing relative to selected urothelial carcinoma-associated genes and circulating tumor DNA analysis.
快速基因组测序技术的发展极大地增进了我们对许多恶性肿瘤分子生物学基础的理解。全外显子组测序突出了恶性肿瘤在患者个体之间的独特性质，并开始彻底改变治疗方法。近年来，尿路上皮恶性肿瘤的全基因组测序已鉴定出大量体细胞突变，这些突变促成了膀胱尿路上皮癌和上尿路尿路上皮癌的生长、进展和转移。随着基因测序的持续进行，将会鉴定出更多靶点，从而能够开发出在分子水平上针对癌症的新型治疗药物，目标是根据患者恶性肿瘤的潜在突变谱提供高度个性化的治疗。在本综述中，我们旨在讨论尿路上皮恶性肿瘤已知的基因改变以及这些突变在预后和靶向治疗药物开发方面的意义。我们将重点关注RNA表达谱分析和基因组DNA分析，尤其关注相对于选定的尿路上皮癌相关基因的全面全外显子组和全基因组测序以及循环肿瘤DNA分析。
