TMPRSS2:ERG Fusion-Associated Deletions Provide Insight into the Heterogeneity of Prostate Cancer

Cancer Research - Tập 66 Số 17 - Trang 8337-8341 - 2006
Sven Perner1,2,3, Francesca Demichelis1,2,4, Rameen Beroukhim2,5,6,7, Folke Schmidt1,2, Juan Miguel Mosquera1,2, Sunita R. Setlur1,2, Joëlle Tchinda1,2, Scott A. Tomlins8,9, Matthias D. Hofer1,2, Kenneth J. Pienta10,11,12, Rainer Kuefer13, Robert L. Vessella14, Xiao Wei Sun1,2, Matthew Meyerson2,5,6,7, Charles Lee1,2, William R. Sellers2,5,6,7, Arul M. Chinnaiyan8,11,9,12, Mark A. Rubin1,2,5
11Department of Pathology, Brigham and Women's Hospital,
2 2Harvard Medical School
34Department of Pathology, University of Ulm;
46Bioinformatics Group, SRA Division, ITC-irst, Trento, Italy;
53Dana-Farber Cancer Institute, Boston, Massachusetts.
67Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts; Departments of
7Departments of
88Pathology,
9Pathology
1010Medical Oncology, University of Michigan, Ann Arbor, Michigan; and
119Urology, and
12Urology, and
135Department of Urology, University Hospital Ulm, Ulm, Germany;
1411University of Washington, Seattle, Washington

Tóm tắt

Abstract Prostate cancer is a common and clinically heterogeneous disease with marked variability in progression. The recent identification of gene fusions of the 5′-untranslated region of TMPRSS2 (21q22.3) with the ETS transcription factor family members, either ERG (21q22.2), ETV1 (7p21.2), or ETV4 (17q21), suggests a mechanism for overexpression of the ETS genes in the majority of prostate cancers. In the current study using fluorescence in situ hybridization (FISH), we identified the TMPRSS2:ERG rearrangements in 49.2% of 118 primary prostate cancers and 41.2% of 18 hormone-naive lymph node metastases. The FISH assay detected intronic deletions between ERG and TMPRSS2 resulting in TMPRSS2:ERG fusion in 60.3% (35 of 58) of the primary TMPRSS2:ERG prostate cancers and 42.9% (3 of 7) of the TMPRSS2:ERG hormone-naive lymph node metastases. A significant association was observed between TMPRSS2:ERG rearranged tumors through deletions and higher tumor stage and the presence of metastatic disease involving pelvic lymph nodes. Using 100K oligonucleotide single nucleotide polymorphism arrays, a homogeneous deletion site between ERG and TMPRSS2 on chromosome 21q22.2-3 was identified with two distinct subclasses distinguished by the start point of the deletion at either 38.765 or 38.911 Mb. This study confirms that TMPRSS2:ERG is fused in approximately half of the prostate cancers through deletion of genomic DNA between ERG and TMPRSS2. The deletion as cause of TMPRSS2:ERG fusion is associated with clinical features for prostate cancer progression compared with tumors that lack the TMPRSS2:ERG rearrangement. (Cancer Res 2006; 66(17): 8337-41)

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Cancer Research

Tập 66 Số 17

8337-8341

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