N-myc downstream regulated gene 1 (NDRG1) is fused to ERG in prostate cancer.

TitleN-myc downstream regulated gene 1 (NDRG1) is fused to ERG in prostate cancer.
Publication TypeJournal Article
Year of Publication2009
AuthorsPflueger D, Rickman DS, Sboner A, Perner S, Lafargue CJ, Svensson MA, Moss BJ, Kitabayashi N, Pan Y, de la Taille A, Kuefer R, Tewari AK, Demichelis F, Chee MS, Gerstein MB, Rubin MA
Date Published2009 Aug
KeywordsAndrogen Antagonists, Base Sequence, Cell Cycle Proteins, Estradiol, Estrogens, Flutamide, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Fluorescence, Intracellular Signaling Peptides and Proteins, Male, Molecular Sequence Data, Oncogene Proteins, Fusion, Prostatic Neoplasms, Reverse Transcriptase Polymerase Chain Reaction, Trans-Activators, Tumor Markers, Biological

A step toward the molecular classification of prostate cancer was the discovery of recurrent erythroblast transformation-specific rearrangements, most commonly fusing the androgen-regulated TMPRSS2 promoter to ERG. The TMPRSS2-ERG fusion is observed in around 90% of tumors that overexpress the oncogene ERG. The goal of the current study was to complete the characterization of these ERG-overexpressing prostate cancers. Using fluorescence in situ hybridization and reverse transcription-polymerase chain reaction assays, we screened 101 prostate cancers, identifying 34 cases (34%) with the TMPRSS2-ERG fusion. Seven cases demonstrated ERG rearrangement by fluorescence in situ hybridization without the presence of TMPRSS2-ERG fusion messenger RNA transcripts. Screening for known 5' partners, we determined that three cases harbored the SLC45A3-ERG fusion. To discover novel 5' partners in these ERG-overexpressing and ERG-rearranged cases, we used paired-end RNA sequencing. We first confirmed the utility of this approach by identifying the TMPRSS2-ERG fusion in a known positive prostate cancer case and then discovered a novel fusion involving the androgen-inducible tumor suppressor, NDRG1 (N-myc downstream regulated gene 1), and ERG in two cases. Unlike TMPRSS2-ERG and SCL45A3-ERG fusions, the NDRG1-ERG fusion is predicted to encode a chimeric protein. Like TMPRSS2, SCL45A3 and NDRG1 are inducible not only by androgen but also by estrogen. This study demonstrates that most ERG-overexpressing prostate cancers harbor hormonally regulated TMPRSS2-ERG, SLC45A3-ERG, or NDRG1-ERG fusions. Broader implications of this study support the use of RNA sequencing to discover novel cancer translocations.

Alternate JournalNeoplasia
PubMed ID19649210
PubMed Central IDPMC2713587
Grant ListR01 CA125612 / CA / NCI NIH HHS / United States
R44HG004237 / HG / NHGRI NIH HHS / United States
RR19895 / RR / NCRR NIH HHS / United States