前列腺癌组织中TMPRSS2基因与ETS家族基因的多种融合亚型及其意义  

Frequency and transcript variant analysis of gene fusions between TMPRSS2 and ETS transcription factor genes in prostate cancer

作　　者：戴美洁[1] 陈俐丽[1] 郑彦博[1] 陈伟[2] 陶志华[1] 翁志梁[2] 吴秀玲[3] 李澄棣[2] 陈占国[1] 陈晓东[1] 石少波[1] 

机构地区：[1]温州医学院附属第一医院实验诊断中心,325000 [2]温州医学院附属第一医院泌尿外科,325000 [3]温州医学院附属第一医院病理科,325000

出　　处：《中华医学杂志》2008年第10期669-673,共5页National Medical Journal of China

摘　　要：目的了解前列腺癌组织标本中跨膜丝氨酸蛋白酶2（TMPRSS2）基因与ETS转录因子家族成员ETS相关基因（ERG）、ETS变异体1（ETV1）及ETS变异体4（ETV4）基因之间的融合情况及意义。方法采用巢式逆转录聚合酶链反应（RT—PCR）琼脂糖凝胶电泳法检测32例前列腺癌患者及34例前列腺良性增生患者前列腺组织中TMPRSS2基因与ETS家族基因融合的TMPRSS2／ERG、TMPRSS2／ETV1、TMPRSS2／ETV4转录体；琼脂糖凝胶电泳阳性者，纯化PCR产物进行直接测序，用BLAST在线软件比对确定融合位点；分析融合基因与Gleason分级关系。结果在32例前列腺癌患者组织标本中，检测到TMPRSS2／ERG融合基因17例（53．1％），含5种不同融合基因亚型，其中1种为新发现融合基因亚型（GenBank登录号：EU090248），单一标本中可检测到1种以上TMPRSS2／ERG融合基因亚型；检测到TMPRSS2／ETV1融合基因2例（6．3％），为新发现融合基因亚型（GenBank登录号：EU090249）；未检到TMPRSS2／ETV4融合基因型。34例前列腺良性增生组织标本中均未检测到TMPRSS2／ERG、TMPRSS2／ETV1和TMPRSS2／ETV4融合基因型。按Gleason评分值分为中分化与低分化的两组前列腺癌组织标本之间融合基因阳性率差异无统计学意义（P=0．169）。结论前列腺癌组织中存在TMPRSS2／ERG和TMPRSS2／ETV1融合基因及多种亚型；前列腺癌融合基因的发现有望为前列腺癌的发病机制研究提供新的思路。Objective To investigate the frequencies and types of fusions between the transmembrane protease serine 2 （TMPRSS2）, ETS-related gene （ERG）, ETS variant-1 （ETV1）, and ETS variant-4 （ETV4） genes in prostate cancer （PCa） and significance thereof. Methods Biopsy samples of prostate were obtained under transrectal ultrasound （TRUS） from 32 PCa patients, aged （74 ± 8） and 34 patients with benign prostate hyperplasia （BPH）. Nested RT-PCR and direct DNA sequencing were used to detect the fusion genes of TMPRSS2/ERG, TMPRSS2/ETV1, and TMPRSS2/ETV4. The association between the fusion-positive tumor rate and Gleason grading was analyzed. Results Of the 32 PCa patients, TMPRSS2/ERG fusion was detected in 17 eases （53. 1% ）, including 5 variant fusion transcrips one of which was newly discovered with the GenBank accession number of EU090248 . TMPRSS2/ETV1 fusion was detected in only 2 cases （6. 3% ）, including one newly discovered variant fusion transcrips with the GenBank accession number of EU090249. TMPRSS2/ETV4 fusion was not detected. The positive rates of TMPRSS2/ERG and TMPRSS2/ETV1 fusions showed no statistical association with the Gleason grade （P = 0. 169）. No fusion between the TMPRSS2 and ETS transcription factor genes was detected in the 34 BPH samples. Condusion TMPRSS2/ERG and TMPRS22/ETV1 fusion genes with different subtypes exist in the tissues of PCa. TMPRSS2/ERG and TMPRSS2/ETV1 fusion genes may be used as diagnostic tools for PCa.

关 键 词：前列腺肿瘤 基因融合 逆转录聚合酶链反应 ETS 跨膜丝氨酸蛋白酶2 

分 类 号：R686[医药卫生—骨科学]