Perner S, Schmidt F H, Hofer M D, Kuefer R, Rubin M
Department of Pathology, Brigham & Women's Hospital/Harvard Medical School, 221 Longwood Avenue, EBRC 442A, Boston, MA 02115-6110, USA.
Urologe A. 2007 Jul;46(7):754-60. doi: 10.1007/s00120-007-1347-0.
Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. Using a novel bioinformatics approach, our group recently described a novel gene fusion in PCa. This fusion involves the androgen-regulated gene TMPRSS2 and so far three members of the ETS family of transcription factors already described as rearranged in the Ewing's family of tumors. By analogy, fusion status in prostate cancer may determine clinical outcome and secondary genetic alterations as witnessed in Ewing's tumors.
These novel gene fusions occur in the majority of prostate cancers identified by PSA screening and are the driving mechanism for overexpression of the three members of the ETS transcription factor family, either ERG (21q22.3), ETV1 (7p21.2), or ETV4 (17q21). Considering the high incidence of prostate cancer and the high frequency of this gene fusion, the TMPRSS2-ETS gene fusion is the most common genetic aberration so far described in human malignancies.
So far, this is the only gene rearrangement in any of the most prevalent cancers. As confirmed by other groups, we demonstrated that, within the group of ETS transcription factors, ERG is the most common fusion partner of the ETS genes with TMPRSS2. This gene fusion is considered to be an early event in PCa development. Emerging data suggest that gene fusion PCa demonstrates a distinct clinical course and thus support its use as a diagnostic test and prognostic biomarker. Also similar to the Philadelphia chromosome in chronic myelogenous leukemia (CML), the gene fusion in prostate cancer has potential as an important candidate for the development of targeted therapy.
常见癌症中反复出现的染色体重排尚未得到充分表征。利用一种新的生物信息学方法，我们团队最近在前列腺癌中描述了一种新的基因融合。这种融合涉及雄激素调节基因TMPRSS2，以及迄今为止已被描述在尤因氏肿瘤家族中发生重排的ETS转录因子家族的三个成员。类推而言，前列腺癌中的融合状态可能决定临床结果和继发性基因改变，这在尤因氏肿瘤中已得到证实。
这些新的基因融合发生在大多数通过前列腺特异性抗原（PSA）筛查发现的前列腺癌中，并且是ETS转录因子家族三个成员（即ERG（21q22.3）、ETV1（7p21.2）或ETV4（17q21））过表达的驱动机制。考虑到前列腺癌的高发病率以及这种基因融合的高频率，TMPRSS2-ETS基因融合是迄今为止在人类恶性肿瘤中描述的最常见的基因畸变。
到目前为止，这是任何一种最常见癌症中唯一的基因重排。正如其他团队所证实的，我们证明，在ETS转录因子组中，ERG是ETS基因与TMPRSS2最常见的融合伴侣。这种基因融合被认为是前列腺癌发展中的早期事件。新出现的数据表明，基因融合型前列腺癌表现出独特的临床病程，因此支持将其用作诊断测试和预后生物标志物。同样类似于慢性粒细胞白血病（CML）中的费城染色体，前列腺癌中的基因融合有潜力成为靶向治疗开发的重要候选对象。
