肾细胞癌VHL基因突变及异常甲基化的临床评价

 目的 评价ＶＮＬ基因异常在肾癌发生发展中的作用及其临床意义。方法 采用聚合酶链反应（ＰＣＲ）加单链构象多态性分析（ＳＳＣＰ）及多重对照聚合酶链反应（Ｍｕｌｔｉｐｌｘ－ＰＣＲ）检测 ４２例肾细胞癌组织、１８例远离肿瘤的正常肾脏及１０例正常肾脏组织中ＶＨＬ基因的突变、异常甲基化。结果１６／２８例（５７．１％）肾透明细胞癌、ＶＳ例（５０％）混合细胞癌中存在 ＶＨＬ基因突变，６／２８例（２１．４％）肾透明细胞癌、１／８例（１２．５％）混合细胞癌中存在异常甲基化，１例远离肿瘤的正常肾脏组织发现ＶＨＬ基因异常甲基化和１例肾透明细胞癌同时存在ＶＨＬ基因突变及异常甲基化；ＶＨＬ基因失活与肾癌组织类型及临床分期相关，与病理分级无关。结论 ＶＨＬ基因的检测可作为肾透明细胞癌的诊断指标，ＶＨＬ基困可望成为肾透明细胞癌基因治疗的重要目的基因。

The mutation and abnormal methylation of VHL tumor-suppressor gene in primary renal cell carcinoma

Objective To evaluate the clinical implications of abnormality of VHL gene in primary renal cell carcinoma(RCC). Methods The mutation and abnormal methylation of VHL gene were detected by Multiplex-PCR, PCR-SSCP in 42 cases primary RCC, 18 cases of normal renal tissues adjacent to neoplas- tic leisons and 10 cases normal renal tissues. Results Mutation of VHL gene was found in 16/28 of Clear RCC, 4/8 of mixed RCC(clear/granular). Abnormal methylation was identified in 6/28 of Clear RCC, 1/ 8 of mixed RCC and 1 of adjacent normal renal tissue. Mutation coexited with Abnormal methylation in 1 Clear RCC. The alteration rate of VHL gene was higher in RCC than in normal renal tissue(P<0. 005), and correlated with the pathological type and stage of patients, with no significant difference between grade of patients. Conclusion VHL gene abnormalities may play a critical role in renal cell tumorigenesis, It could be used as a predictor of early diagnosis of cRCC and for genetherapy to cRCC.