PMID- 19773449
OWN - NLM
STAT- MEDLINE
DCOM- 20091203
LR  - 20211020
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 69
IP  - 19
DP  - 2009 Oct 1
TI  - Comparative analyses of chromosome alterations in soft-tissue metastases within 
      and across patients with castration-resistant prostate cancer.
PG  - 7793-802
LID - 10.1158/0008-5472.CAN-08-3810 [doi]
AB  - Androgen deprivation is the mainstay of therapy for progressive prostate cancer. 
      Despite initial and dramatic tumor inhibition, most men eventually fail therapy 
      and die of metastatic castration-resistant (CR) disease. Here, we characterize 
      the profound degree of genomic alteration found in CR tumors using array 
      comparative genomic hybridization (array CGH), gene expression arrays, and 
      fluorescence in situ hybridization (FISH). Bycluster analysis, we show that the 
      similarity of the genomic profiles from primary and metastatic tumors is driven 
      by the patient. Using data adjusted for this similarity, we identify numerous 
      high-frequency alterations in the CR tumors, such as 8p loss and chromosome 7 and 
      8q gain. By integrating array CGH and expression array data, we reveal genes 
      whose correlated values suggest they are relevant to prostate cancer biology. We 
      find alterations that are significantly associated with the metastases of 
      specific organ sites, and others with CR tumors versus the tumors of patients 
      with localized prostate cancer not treated with androgen deprivation. Within the 
      high-frequency sites of loss in CR metastases, we find an overrepresentation of 
      genes involved in cellular lipid metabolism, including PTEN. Finally, using FISH, 
      we verify the presence of a gene fusion between TMPRSS2 and ERG suggested by 
      chromosome 21 deletions detected by array CGH. We find the fusion in 54% of our 
      CR tumors, and 81% of the fusion-positive tumors contain cells with multiple 
      copies of the fusion. Our investigation lays the foundation for a better 
      understanding of and possible therapeutic targets for CR disease, the poorly 
      responsive and final stage of prostate cancer.
FAU - Holcomb, Ilona N
AU  - Holcomb IN
AD  - Divisions of Human Biology, Fred Hutchinson Cancer Research Center, University of 
      Washington, Seattle, Washington, USA.
FAU - Young, Janet M
AU  - Young JM
FAU - Coleman, Ilsa M
AU  - Coleman IM
FAU - Salari, Keyan
AU  - Salari K
FAU - Grove, Douglas I
AU  - Grove DI
FAU - Hsu, Li
AU  - Hsu L
FAU - True, Lawrence D
AU  - True LD
FAU - Roudier, Martine P
AU  - Roudier MP
FAU - Morrissey, Colm M
AU  - Morrissey CM
FAU - Higano, Celestia S
AU  - Higano CS
FAU - Nelson, Peter S
AU  - Nelson PS
FAU - Vessella, Robert L
AU  - Vessella RL
FAU - Trask, Barbara J
AU  - Trask BJ
LA  - eng
GR  - R01DC004209/DC/NIDCD NIH HHS/United States
GR  - R01 CA098415/CA/NCI NIH HHS/United States
GR  - P50 CA097186/CA/NCI NIH HHS/United States
GR  - T32 HG000035-07/HG/NHGRI NIH HHS/United States
GR  - U24 CA80295/CA/NCI NIH HHS/United States
GR  - R01 DC004209-10/DC/NIDCD NIH HHS/United States
GR  - P01 CA085859/CA/NCI NIH HHS/United States
GR  - R01 DK069690/DK/NIDDK NIH HHS/United States
GR  - R01 CA095717-04/CA/NCI NIH HHS/United States
GR  - R01CA098415/CA/NCI NIH HHS/United States
GR  - R01 DK069690-04/DK/NIDDK NIH HHS/United States
GR  - R01 CA95717/CA/NCI NIH HHS/United States
GR  - R01 CA095717/CA/NCI NIH HHS/United States
GR  - T32 GM007365/GM/NIGMS NIH HHS/United States
GR  - CA97186/CA/NCI NIH HHS/United States
GR  - R01 AG014358/AG/NIA NIH HHS/United States
GR  - R01 AG14358/AG/NIA NIH HHS/United States
GR  - U24 CA080295-03S1/CA/NCI NIH HHS/United States
GR  - R01 GM07365/GM/NIGMS NIH HHS/United States
GR  - R01 CA098415-05/CA/NCI NIH HHS/United States
GR  - R01 DC004209/DC/NIDCD NIH HHS/United States
GR  - R01 AG014358-09/AG/NIA NIH HHS/United States
GR  - T32 HG000035/HG/NHGRI NIH HHS/United States
GR  - T32 HG00035/HG/NHGRI NIH HHS/United States
GR  - P50 CA097186-089001/CA/NCI NIH HHS/United States
GR  - P01 CA085859-05S1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090922
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (TMPRSS2-ERG fusion protein, human)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - *Chromosome Aberrations
MH  - Cluster Analysis
MH  - Comparative Genomic Hybridization
MH  - Gene Dosage
MH  - Gene Expression Profiling
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/genetics
MH  - Orchiectomy
MH  - Prostatic Neoplasms/*genetics/pathology/surgery
MH  - Soft Tissue Neoplasms/*genetics/*secondary
PMC - PMC2771763
MID - NIHMS140234
EDAT- 2009/09/24 06:00
MHDA- 2009/12/16 06:00
PMCR- 2010/10/01
CRDT- 2009/09/24 06:00
PHST- 2009/09/24 06:00 [entrez]
PHST- 2009/09/24 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - 0008-5472.CAN-08-3810 [pii]
AID - 10.1158/0008-5472.CAN-08-3810 [doi]
PST - ppublish
SO  - Cancer Res. 2009 Oct 1;69(19):7793-802. doi: 10.1158/0008-5472.CAN-08-3810. Epub 
      2009 Sep 22.