Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer
Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer
复制标题
DOI：
10.1038/modpathol.3800769
复制
发表时间：
2007-05-01
期刊：
影响因子：
7.5
通讯作者：
Shah, Rajal B.
中科院分区：
文献类型：
--
作者：
Mehra, Rohit;Tomlins, Scott A.;Shah, Rajal B.
雄激素调节基因TMPRSS 2和ETS家族成员ERG、ETV 1或ETV 4之间的新的复发性基因融合最近已被鉴定为前列腺癌发展中的常见分子事件。我们综合分析了96名因临床局限性前列腺癌而接受手术治疗的美国男性患者的TMPRSS 2和ETS家族基因重排的频率和疾病进展风险。使用三个分离（TMPRSS 2，ERG，ETV 4）和一个融合（TMPRSS：ETV 1）荧光原位杂交（FISH）检测，我们确定重排TMPRSS 2，ERG，ETV 1，和ETV 4的情况下，分别为65，55，2，和2%。总体而言，分别有54%和2%的病例显示TMPRSS 2：ERG和TMPRSS 2：ETV 1融合。由于TMPRSS 2和ERG之间基因组DNA的内含子丢失已被鉴定为TMPRSS 2：ERG融合的机制，我们的测定允许我们在41%和39%的相应基因重排的病例中检测TMPRSS 2的30端和ERG的50端的缺失。TMPRSS 2基因重排的前列腺癌与高病理分期相关（P = 0.04）。我们的研究结果证实，TMPRSS 2和/或ETS家族成员中的复发性染色体畸变在约70%的前列腺癌中发现。重要的是，我们定义了一种新的方法来研究这些基因融合，并确定了TMPRSS 2重排而没有ERG，ETV 1或ETV 4重排的病例和ETS家族基因重排而没有TMPRSS 2重排的病例，这表明新的50和30个伴侣可能参与前列腺癌的基因融合。
Novel recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, or ETV4 have been recently identified as a common molecular event in prostate cancer development. We comprehensively analyzed the frequency and risk of disease progression for the TMPRSS2 and ETS family genes rearrangements in a cohort of 96 American men surgically treated for clinically localized prostate cancer. Using three break apart ( TMPRSS2, ERG, ETV4) and one fusion (TMPRSS: ETV1) fluorescence in situ hybridization ( FISH) assays, we identified rearrangements in TMPRSS2, ERG, ETV1, and ETV4 in 65, 55, 2, and 2% of cases, respectively. Overall, 54 and 2% of cases demonstrated TMPRSS2: ERG and TMPRSS2: ETV1 fusions, respectively. As intronic loss of genomic DNA between TMPRSS2 and ERG has been identified as a mechanism of TMPRSS2: ERG fusion, our assays allowed us to detect deletion of the 30 end of TMPRSS2 and the 50 end of ERG in 41 and 39% of cases rearranged for respective genes. Prostate cancers demonstrating TMPRSS2 gene rearrangement were associated with high pathologic stage (P = 0.04). Our results confirm that recurrent chromosomal aberrations in TMPRSS2 and/or ETS family members are found in about 70% of prostate cancers. Importantly, we define a novel approach to study these gene fusions and identified cases where TMPRSS2 was rearranged without rearrangement of ERG, ETV1 or ETV4 and cases with ETS family gene rearrangement without TMPRSS2 rearrangement, suggesting that novel 50 and 30 partners may be involved in gene fusions in prostate cancer.