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

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.