Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
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DOI：
10.1016/j.ccell.2016.05.004
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发表时间：
2016-07-11
期刊：
影响因子：
50.3
通讯作者：
Dyrskjot, Lars
中科院分区：
文献类型：
--
作者：
Hedegaard, Jakob;Lamy, Philippe;Dyrskjot, Lars
非肌肉浸润性膀胱癌（NMIBC）是一种异质性疾病，具有广泛的不同结果。我们对460例早期尿路上皮癌进行了全面的转录分析，结果表明，NMIBC可以分为三个主要类别，具有基底和管腔样特征和不同的临床结果。观察到生物学过程如细胞周期、上皮-间充质转化和分化的巨大差异。转录变体的分析揭示了在编码参与染色质组织和细胞骨架功能的蛋白质的基因中的频繁突变。此外，众所周知的癌症驱动基因（例如，TP 53和ERBB 2）主要在高风险肿瘤中发现，以及APOBEC相关的突变特征。NMIBC亚类的识别可以提供更好的说明和基于亚类分配的治疗选择。
Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.