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肾细胞癌中肿瘤抑制基因的异常甲基化

[Aberrant methylation of tumor suppressor genes in renal cell carcinoma].

作者信息

Zhang Qian, Jin Jie, Tao Qian

机构信息

Department of Urology, Institute of Urology, The First Hospital, Peking University, Beijing, 100034, PR China.

出版信息

Ai Zheng. 2007 Nov;26(11):1276-80.

Abstract

Promoter CpG methylation is a major epigenetic mechanism to inactivate the functions of tumor suppressor genes (TSG), in addition to genetic mechanism (point mutation and deletion), plays important roles in the pathogenesis of various tumors. Renal cell carcinoma (RCC) is a malignant tumor with poor prognosis, in which aberrant methylation of TSGs has also been widely reported. Most RCC patients are presented with advanced disease because early stage RCC does not have apparent symptoms. The detection of TSG methylation might provide new specific biomarkers for early non-invasive diagnosis of this disease. Because RCC is generally insensitive to conventional chemotherapy and radiotherapy, using epigenetic agents, such as azacytidine, to modulate the activities of DNA methyltransferases and reverse the methylation status of TSGs might be an attractive strategy for future treatment of RCC, which could be combined with conventional therapies. We reviewed recent advances in the research on TSG methylation in RCC, summarized the methylation profile of RCC-related genes, including HOXB13, HAI2/SPINT2, CDH1 and CTNNG/JUP, and discussed the clinical significance of aberrant CpG methylation for the diagnosis and treatment of RCC.

摘要

启动子CpG甲基化是使肿瘤抑制基因(TSG)功能失活的主要表观遗传机制,除了遗传机制(点突变和缺失)外,在各种肿瘤的发病机制中也起着重要作用。肾细胞癌(RCC)是一种预后较差的恶性肿瘤,其中TSG的异常甲基化也有广泛报道。大多数RCC患者就诊时已处于疾病晚期,因为早期RCC没有明显症状。检测TSG甲基化可能为该疾病的早期非侵入性诊断提供新的特异性生物标志物。由于RCC通常对传统化疗和放疗不敏感,使用表观遗传药物,如阿扎胞苷,来调节DNA甲基转移酶的活性并逆转TSG的甲基化状态可能是未来RCC治疗的一个有吸引力的策略,可与传统疗法联合使用。我们综述了RCC中TSG甲基化研究的最新进展,总结了RCC相关基因的甲基化谱,包括HOXB13、HAI2/SPINT2、CDH1和CTNNG/JUP,并讨论了异常CpG甲基化对RCC诊断和治疗的临床意义。

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