Rubin Mark A, Chinnaiyan Arul M
Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115-6110, USA.
Lab Invest. 2006 Nov;86(11):1099-102. doi: 10.1038/labinvest.3700477. Epub 2006 Sep 18.
Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We describe the use of a novel bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression called COPA (cancer outlier profile analysis). We demonstrate how this approach led to the identification of gene fusions of the 5'-untranslated region of TMPRSS2 (21q22.3), an androgen regulated gene, with the ETS transcription factor family members, either ERG (21q22.2), ETV1 (7p21.2), or ETV4(17q21). These novel gene fusions suggest a mechanism for overexpression of the ETS genes in the majority of prostate cancers identified through PSA screening. Considering the high incidence of prostate cancer and the high frequency of this gene fusion, the TMPRSS2-ETS gene fusions are the most common genetic aberration so far described in human malignancies. The clinical implications of this discovery are significant for diagnosis and potentially for the development of targeted therapy.
复发性染色体重排在常见癌症中尚未得到充分表征。我们描述了一种新型生物信息学方法的应用，该方法基于称为COPA（癌症异常值谱分析）的异常基因表达来发现候选致癌染色体畸变。我们展示了这种方法如何导致鉴定出雄激素调节基因TMPRSS2（21q22.3）5'非翻译区与ETS转录因子家族成员ERG（21q22.2）、ETV1（7p21.2）或ETV4（17q21）的基因融合。这些新型基因融合提示了通过PSA筛查在大多数前列腺癌中ETS基因过表达的一种机制。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遗传畸变。这一发现的临床意义对于诊断以及潜在的靶向治疗开发都很重要。
