53例国人肾透明细胞癌中PBRM 1基因的突变分析

目的 分析Polybromo 1（PBRM 1）基因在国人肾透明细胞癌中的突变特点，探讨基因突变与临床病理特征和预后的关系。方法 选取53例肾透明细胞癌患者，利用PCR结合直接测序的方法检测PBRM 1基因2～5号外显子、15～17号外显子的突变情况。分析PBRM 1基因突变与临床病理特征和预后的相关性。结果 53例样本中检测出PBRM 1基因突变14例，突变率为26％。突变较集中分布在第15、17外显子，第15外显子5例，第17外显子6例。PBRM 1基因突变组和无突变组的中位无进展生存期分别为5个月（95％CI：1.6～8.4个月）和14个月（95％CI：9.7～18.3个月），中位生存期分别为7个月（95％CI：2.6～11.4个月）和18个月（95％CI：5.6～30.4个月），差异均有统计学意义（P＜0.05）。 PBRM 1基因突变与性别、年龄、发病部位、分期及疾病控制率等无关（P＞0.05）。结论 中国人肾透明细胞癌中PBRM 1基因突变率较高，突变主要位于第15、17外显子。PBRM 1基因突变可能是肾透明细胞癌患者预后不良的危险因素。

Analysis of PBRM 1 gene mutations in 53 Chinese patients with clear cell renal cell carcinoma

Objective To determine the characteristics of polybromo 1（PBRM 1） gene mutations of clear cell renal cell carcinoma in the Chinese populations and further analyze the correlations between PBRM1 gene mutations and the clinical parameters.Methods Mutations were detected in exons 2-5 and exon 15-17 of PBRM 1 in genomic DNA of 53 clear cell renal cell carcinomas by PCR amplification and sanger direct sequencing,and correlations were analyzed among the mutations and the clinical parameters.Results Mutations were detected in 14 of 53 clear cell renal cell carcinomas（26%）.Eleven of 14 mutations were in the region of exon 15 and exon 17,5 in exon 15 and 6 in exon 17.The median progress free survival in mutation group and non-mutation group was 5 months（95%CI：1.6-8.4 months） and 14 months（95%CI：9.7-18.3 months）,and the median overall survival was 7 months（95%CI：2.6-11.4months） and 18 months（95%CI：5.6-30.4months）,with statistical significance（P〈0.05）.No significant differences were observed between mutations and the other various clinical parameters,such as gender,age,tumor position,stage and the disease control rate.Conclusion The percentage of PBRM 1 gene mutations is higher in Chinese patients with clear cell renal cell carcinoma.Mutations are mainly located in the exon 15 and exon 17.PBRM1 gene mutation may be a factor of poor prognosis.