Kang Ho Won, Kim Wun-Jae, Choi Woonyoung, Yun Seok Joong
Department of Urology, School of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Korea.
Department of Urology, Chungbuk National University Hospital, Cheongju, Korea.
Transl Androl Urol. 2020 Dec;9(6):2866-2880. doi: 10.21037/tau.2020.03.13.
Muscle-invasive bladder cancer (MIBC), a highly heterogeneous disease, shows genomic instability and a high mutation rate. Clinical outcomes are variable and responses to conventional chemotherapy differ among patients (due to inter-patient tumor heterogeneity and inter-tumor heterogeneity) and even within each individual tumor (intra-tumor heterogeneity). Emerging evidence indicates that tumor heterogeneity may play an important role in cancer progression, resistance to therapy, and metastasis. Comprehensive molecular subtyping classifies MIBC into distinct categories that have potential to guide prognosis, patient stratification, and treatment. Genomic characterization of time-series analyses at the single cell level, and of cell-free circulating tumor DNA or circulating tumor cells, are emerging technologies that enable dissection of the complex clonal architecture of MIBC. This review provides insight into the clinical significance of the molecular mechanisms underlying heterogeneity, focusing on inter- and intra-tumor heterogeneity, with special emphasis on molecular classification and methods used to analyze the complex patterns involved.
肌肉浸润性膀胱癌（MIBC）是一种高度异质性疾病，表现出基因组不稳定和高突变率。临床结果存在差异，患者对传统化疗的反应也各不相同（由于患者间肿瘤异质性和肿瘤间异质性），甚至在每个肿瘤内部也存在差异（肿瘤内异质性）。新出现的证据表明，肿瘤异质性可能在癌症进展、治疗耐药性和转移中起重要作用。综合分子亚型分类将MIBC分为不同类别，这些类别有可能指导预后、患者分层和治疗。单细胞水平的时间序列分析以及游离循环肿瘤DNA或循环肿瘤细胞的基因组特征分析，是新兴技术，能够剖析MIBC复杂克隆结构。本综述深入探讨了异质性潜在分子机制的临床意义，重点关注肿瘤间和肿瘤内异质性，特别强调分子分类以及用于分析所涉及复杂模式的方法。
