title: TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer.
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.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, EBRC 442A, 221 Longwood Avenue, Boston, MA 02115-6110, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.forename: Folke H
authors.initials: FH
authors.lastname: Schmidt
authors.forename: Juan-Miguel
authors.initials: JM
authors.lastname: Mosquera
authors.forename: Sunita
authors.initials: S
authors.lastname: Setlur
authors.forename: Joelle
authors.initials: J
authors.lastname: Tchinda
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.forename: Matthias D
authors.initials: MD
authors.lastname: Hofer
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Pienta
authors.forename: Rainer
authors.initials: R
authors.lastname: Kuefer
authors.forename: Robert
authors.initials: R
authors.lastname: Vessella
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Sun
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: William R
authors.initials: WR
authors.lastname: Sellers
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D020121:5' Untranslated Regions; D045744:Cell Line, Tumor; D017353:Gene Deletion; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human