肾透明细胞癌中VHL基因失活的检测及意义

目的 探讨肾透明细胞癌中Von Hippel-Lindau(VHL)基因突变和超甲基化情况及其在肾癌发生发展中的作用及临床意义.方法 采用聚合酶链反应-单链构象多态性分析(PCRSSCP)银染法,甲基化特异性PCR(MSP)及测序等方法对33例肾透明细胞癌和相应远离肿瘤正常肾组织VHL基因突变和超甲基化情况进行检测.结果 19/33(57.6%)例肾透明细胞癌中出现VHL基因突变;6/33(18.2%)例肾透明细胞癌中出现VHL基因超甲基化;VHL基因突变和超甲基化与肾癌临床分期和淋巴结转移相关.结论 肾癌中存在VHL基因突变和超甲基化,且与临床分期、淋巴结转移相关;VHL基因失活的检测可作为肾透明细胞癌的诊断指标,VHL基因可望成为肾透明细胞癌基因治疗的重要目的 基因.

The mutation and hyper-methylation of Yon Hippel-Lindau tumor-suppressor gene in tumor tissue and urine from kidney cancer patients

Objective To investigate the clinical implications of mutation and hyper-methylation of VHL gene,and analyze its relationships with pathological stage,grade,lymph node metastasis,the pathological type,size of tumor and age of patients with renal cell carcinoma (RCC).Methods Silver staining of single-strand conformation polymorphism of polymerase chain reaction ( PCR-SSCP),methylation-specific PCR (MSP) and direct sequencing were used to examine the mutation and the methylation status of promter of VHL gene in 33 cases of primary sporadic RCC and adjacent nonmalignant renal tissues.Results Somatic mutation of VHL gene was detected in 19 (57.6%) of the 33 cases of RCC.Hyper-methylation of promter of VHL gene was detected in 6 ( 18.2% ) of 33 cases of RCC.Statistical analysis showed that mutation and hyper-methylation of VHL gene were significantly correlated with the stage of RCC and the lymph node metastasis.Conclusion There are frequent mutations and hyper-methylations of VHL in primary sporadic Chinese RCC.VHL gene abnormalities may play a critical role in diagnosis of RCC.VHL gene can be used as a predictor of early diagnosis of RCC and a target one of gene therapy for RCC.