Re: Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.

摘要

Using a novel technique the "cancer outlier profile analysis" (COPA), the authors identified the ERG and ETV1 genes as being most frequently overexpressed to show gene rearrangements in prostate cancer. To achieve this goal, COPA was applied to the "onco-mine database," a compendium of gene expression data sets representing a large number of DNA micro-array experiments. The ERG and ETC1 genes ranked in the top 10 outlier profiles of this database. The authors then determined the mechanism of ERG and ETV1 overexpression. Complete transcripts of over-expressed ETV1 and ERG were obtained from lymph node prostate cancer cells (LNCaP) and from the nodal metastases MET26-LN (ETV1) and MET28-LN (ERG). Fusions of both genes with the well-known pro state-specific gene TMPRSS2 were demonstrated. TMPRSS2 contains an androgen-responsive element (ARE). In a series of prostate cancer cell lines, prostate cancer tissues, and benign prostatic tissues the presence of the fusion genes was then studied by polymerase chain reaction techniques. Overexpression of the ERG and ETV1 fusion genes was mutually exclusive in prostate cancers and lines and absent in normal prostatic tissue. The fusions were only found in samples that overexpressed ERG or ETV1. The presence of either of these fusions was confirmed by fluorescence in situ hybridisation in 23 of 29 cases studied (79.3%). The'authors then showed that TMPRSS2/ERG fusion results in androgenic reg- ulation of the expression of the ERG gene in the LNCaP cell line.