Molecular genetics of bladder cancer: Emerging mechanisms of tumor initiation and progression.
Molecular genetics of bladder cancer: Emerging mechanisms of tumor initiation and progression.
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DOI：
10.1016/j.urolonc.2010.04.008
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发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Czerniak B
中科院分区：
文献类型：
--
作者：
McConkey DJ;Lee S;Choi W;Tran M;Majewski T;Lee S;Siefker-Radtke A;Dinney C;Czerniak B
尿路上皮癌一直是有关人类实体恶性肿瘤发生发展的突变事件的最重要信息来源之一。尽管影响整个膀胱黏膜的“场效应”似乎引发了疾病，但肿瘤沿着两种截然不同的生物学“路径”发展，这给临床管理带来了截然不同的挑战。近期的全基因组方法促进了在识别膀胱癌发生和进展所涉及的分子机制方面更为迅速的进展。具体而言，全器官定位结合高分辨率、高通量单核苷酸多态性（SNP）分析已经确定了一类新的候选肿瘤抑制基因（“先驱基因”），它们位于更为熟知的肿瘤抑制基因附近，但在癌症发展的早期阶段就被破坏。此外，全基因组比较基因组杂交（CGH）和信使核糖核酸（mRNA）表达谱分析表明，尿路上皮癌的两种主要亚型（乳头状/浅表性和非乳头状/肌层浸润性）是真正不同的分子实体，并且在近期的研究中，我们的团队发现肌层浸润性肿瘤表达一种被称为“上皮 - 间质转化”（EMT）的发育过程所特有的分子标记。新出现的证据表明，尿路上皮癌包含肿瘤起始细胞（“癌症干细胞”）亚群，但这些细胞在不同肿瘤中的表型是异质的，这引发了关于这两种主要癌症亚型是否具有共同前体的疑问。本综述将概述这些新的见解，并讨论未来研究的重点。
Urothelial cancer has served as one of the most important sources of information about the mutational events that underlie the development of human solid maligancies. Although “field effects” that affect the entire bladder mucosa appear to initiate disease, tumors develop along two distinct biological “tracks” that present vastly different challenges for clinical management. Recent whole genome methodologies have facilitated even more rapid progress in the identification of the molecular mechanisms involved in bladder cancer initiation and progression. Specifically, whole organ mapping combined with high resolution, high throughput SNP analyses have identified a novel class of candidate tumor suppressors (“forerunner genes”) that localize near more familiar tumor suppressors but are disrupted at an earlier stage of cancer development. Furthermore, whole genome comparative genomic hybridization (CGH) and mRNA expression profiling have demonstrated that the two major subtypes of urothelial cancer (papillary/superficial and non-papillary/muscle-invasive) are truly distinct molecular entities, and in recent work our group has discovered that muscle-invasive tumors express molecular markers characteristic of a developmental process known as “epithelial-to-mesenchymal transition” (EMT). Emerging evidence indicates that urothelial cancers contain subpopulations of tumor-initiating cells (“cancer stem cells”) but the phenotypes of these cells in different tumors are heterogeneous, raising questions about whether or not the two major subtypes of cancer share a common precursor. This review will provide an overview of these new insights and discuss priorities for future investigation.
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DOI：
10.1073/pnas.0906549106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Chan, Keith Syson;Espinosa, Inigo;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
6.6
作者：
DINNEY, CPN;FISHBECK, R;KILLION, JJ
通讯作者：
KILLION, JJ
影响因子：
4.6
作者：
Cheng, Wei;Jacobs, W. Bradley;Kim, Peter C. W.
通讯作者：
Kim, Peter C. W.
影响因子：
3.3
作者：
CZERNIAK, B;COHEN, GL;KOSS, LG
通讯作者：
KOSS, LG
影响因子：
158.5
作者：
ESRIG, D;ELMAJIAN, D;COTE, RJ
通讯作者：
COTE, RJ