Department of Preventive Medicine; Keck School of Medicine of USC; University of Southern California; Los Angeles, CA USA.
Epigenetics. 2013 Oct;8(10):1013-22. doi: 10.4161/epi.25927. Epub 2013 Aug 6.
Bladder cancer is the fourth most common cancer in men in the United States, and its recurrence rate is highest among all malignancies. The unmet need for improved strategies for early detection, treatment, and monitoring of the progression of this disease continues to translate into high mortality and morbidity. The quest for advanced diagnostic, therapeutic, and prognostic approaches for bladder cancer is a high priority, which can be achieved by understanding the molecular mechanisms of the initiation and progression of this malignancy. Aberrant DNA methylation in single or multiple cancer-related genes/loci has been found in human bladder tumors and cancer cell lines, and urine sediments, and correlated with many clinicopathological features of this disease, including tumor relapse, muscle-invasiveness, and survival. The present review summarizes the published research on aberrant DNA methylation in connection with human bladder cancer. Representative studies are highlighted to set forth the current state of knowledge, gaps in the knowledgebase, and future directions in this prime epigenetic field of research. Identifying the potentially reversible and 'drugable' aberrant DNA methylation events that initiate and promote bladder cancer development can highlight biological markers for early diagnosis, effective therapy and accurate prognosis of this malignancy.
膀胱癌是美国男性中第四大常见癌症，其复发率在所有恶性肿瘤中最高。人们对改善这种疾病的早期检测、治疗和监测进展的策略的需求仍未得到满足，这导致其死亡率和发病率居高不下。因此，寻求膀胱癌的先进诊断、治疗和预后方法是当务之急，可以通过了解这种恶性肿瘤的发生和发展的分子机制来实现。在人类膀胱癌和癌细胞系以及尿液沉淀物中发现了单个或多个与癌症相关的基因/基因座的异常 DNA 甲基化，并与该疾病的许多临床病理特征相关，包括肿瘤复发、肌肉侵袭和存活。本综述总结了与人类膀胱癌相关的异常 DNA 甲基化的已发表研究。突出显示了代表性研究，以阐述该主要表观遗传学研究领域的现有知识状态、知识库中的空白以及未来方向。确定可能是膀胱癌发生和发展的起始和促进因素的、具有潜在可逆性和“可药物性”的异常 DNA 甲基化事件，可以突出用于这种恶性肿瘤的早期诊断、有效治疗和准确预后的生物标志物。
