肾细胞癌VHL基因突变及异常甲基化的临床评价

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

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。

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.