TY - JOUR
T1 - Molecular characterization of TMPRSS2-ERG gene fusion in the NCI-H660 prostate cancer cell line
T2 - A new perspective for an old model
AU - Mertz, Kirsten D.
AU - Setlur, Sunita R.
AU - Dhanasekaran, Saravana M.
AU - Demichelis, Francesca
AU - Perner, Sven
AU - Tomlins, Scott
AU - Tchinda, Joëlle
AU - Laxman, Bharathi
AU - Vessella, Robert L.
AU - Beroukhim, Rameen
AU - Lee, Charles
AU - Chinnaiyan, Arul M.
AU - Rubin, Mark A.
N1 - Funding Information:
Abbreviations: AR, androgen receptor; FISH, fluorescence in situ hybridization; PrSC, prostate stromal cell; PSA, prostate-specific antigen; qPCR, quantitative polymerase chain reaction; RT-PCR, reverse transcription–polymerase chain reaction; SNP, single-nucleotide polymorphism Address all correspondence to: Mark A. Rubin, MD, Department of Pathology, Brigham and Women’s Hospital/Harvard Medical School, 221 Longwood Avenue, EBRC 442A, Boston, MA 02115-6110. E-mail: [email protected] 1This work was supported by the National Institutes of Health Prostate Specialized Program of Research Excellence (SPORE) at the Dana Farber/Harvard Cancer Center (NCI P50 CA090381) and the University of Michigan (NCI P50 CA69568 and R01AG21404 to M.A.R. and A.M.C.), the Swiss Foundation for Medical–Biological Grants SSMBS (SNF 1168 to K.D.M.), the Prostate Cancer Foundation (to F.D.), Deutsche Forschungsgemeinschaft DFG PE1179 (to S.P.), the Department of Defense Fellowship Awards (PC061474 to S.P. and PC040638 to R.B.), and the NW Prostate Cancer SPORE (to R.L.V.). *This article refers to supplementary material, which is designated by ‘‘W’’ (i.e., Figure W1) and is available online at www.bcdecker.com. Received 4 January 2007; Revised 23 January 2007; Accepted 24 January 2007.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2007/3
Y1 - 2007/3
N2 - Recent studies have established that a significant fraction of prostate cancers harbor a signature gene fusion between the 5′ region of androgen-regulated TMPRSS2 and an ETS family transcription factor, most commonly ERG. Studies on the molecular mechanisms and functional consequences of this important chromosomal rearrangement are currently limited to the VCaP cell line derived from a vertebral bone metastasis of a hormone-refractory prostate tumor. Here we report on the NCI-H660 cell line, derived from a metastatic site of an extrapulmonary small cell carcinoma arising from the prostate. NCI-H660 harbors TMPRSS2-ERG fusion with a homozygous intronic deletion between TMPRSS2 and ERG. We demonstrate this by real-time quantitative polymerase chain reaction, a two-stage dual-color interphase fluorescence in situ hybridization (FISH) assay testing for TMPRSS2 and ERG break-aparts, and single-nucleotide polymorphism oligonucleotide arrays. The deletion is consistent with the common intronic deletion found on chromosome 21q22.2-3 in human prostate cancer samples. We demonstrate the physical juxtaposition of TMPRSS2 and ERG on the DNA level by fiber FISH. The androgen receptor-negative NCI-H660 cell line expresses ERG in an androgen-independent fashion. This in vitro model system has the potential to provide important pathobiologic insights into TMPRSS2-ERG fusion prostate cancer.
AB - Recent studies have established that a significant fraction of prostate cancers harbor a signature gene fusion between the 5′ region of androgen-regulated TMPRSS2 and an ETS family transcription factor, most commonly ERG. Studies on the molecular mechanisms and functional consequences of this important chromosomal rearrangement are currently limited to the VCaP cell line derived from a vertebral bone metastasis of a hormone-refractory prostate tumor. Here we report on the NCI-H660 cell line, derived from a metastatic site of an extrapulmonary small cell carcinoma arising from the prostate. NCI-H660 harbors TMPRSS2-ERG fusion with a homozygous intronic deletion between TMPRSS2 and ERG. We demonstrate this by real-time quantitative polymerase chain reaction, a two-stage dual-color interphase fluorescence in situ hybridization (FISH) assay testing for TMPRSS2 and ERG break-aparts, and single-nucleotide polymorphism oligonucleotide arrays. The deletion is consistent with the common intronic deletion found on chromosome 21q22.2-3 in human prostate cancer samples. We demonstrate the physical juxtaposition of TMPRSS2 and ERG on the DNA level by fiber FISH. The androgen receptor-negative NCI-H660 cell line expresses ERG in an androgen-independent fashion. This in vitro model system has the potential to provide important pathobiologic insights into TMPRSS2-ERG fusion prostate cancer.
UR - http://www.scopus.com/inward/record.url?scp=33947358183&partnerID=8YFLogxK
U2 - 10.1593/neo.07103
DO - 10.1593/neo.07103
M3 - Journal articles
C2 - 17401460
AN - SCOPUS:33947358183
SN - 1522-8002
VL - 9
SP - 200
EP - 206
JO - Neoplasia
JF - Neoplasia
IS - 3
ER -
