PMID- 17804708
OWN - NLM
STAT- MEDLINE
DCOM- 20071030
LR  - 20071203
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 67
IP  - 17
DP  - 2007 Sep 1
TI  - Heterogeneity of TMPRSS2 gene rearrangements in multifocal prostate 
      adenocarcinoma: molecular evidence for an independent group of diseases.
PG  - 7991-5
AB  - Recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS 
      family transcription factors ERG, ETV1, and ETV4 have been identified in the 
      majority of prostate adenocarcinomas (PCA). PCA is often multifocal with 
      histologic heterogeneity of different tumor foci. As TMPRSS2 is a common 5' 
      partner of ETS gene fusions, we monitored TMPRSS2 rearrangement by fluorescence 
      in situ hybridization (FISH) to study the origin and molecular basis of 
      multifocal PCA heterogeneity. TMPRSS2 rearrangement was evaluated by FISH on a 
      tissue microarray representing 93 multifocal PCAs from 43 radical prostatectomy 
      resections. Overall, 70% (30 of 43) of the cases showed TMPRSS2 rearrangement, 
      including 63% through deletion (loss of the 3' TMPRSS2 signal), 27% through 
      translocation (split of 5' and 3' TMPRSS2 signals), and 10% through both 
      mechanisms in different tumor foci. Of the 30 TMPRSS2 rearranged cases, 30% 
      showed concordance in all tumor foci, whereas 70% were discordant in at least one 
      focus. In TMPRSS2 rearranged cases, the largest (index) tumor was rearranged 83% 
      of the time. Pathologic stage, size, or Gleason grade of the multifocal PCA did 
      not correlate with overall TMPRSS2 rearrangement. Our results suggest that 
      multifocal PCA is a heterogeneous group of diseases arising from multiple, 
      independent clonal expansions. Understanding this molecular heterogeneity is 
      critical to the future development and utility of diagnostic and prognostic PCA 
      biomarkers.
FAU - Mehra, Rohit
AU  - Mehra R
AD  - Michigan Center for Translational Pathology, Department of Pathology, University 
      of Michigan Medical School, Ann Arbor, MI 48109, USA.
FAU - Han, Bo
AU  - Han B
FAU - Tomlins, Scott A
AU  - Tomlins SA
FAU - Wang, Lei
AU  - Wang L
FAU - Menon, Anjana
AU  - Menon A
FAU - Wasco, Matthew J
AU  - Wasco MJ
FAU - Shen, Ronglai
AU  - Shen R
FAU - Montie, James E
AU  - Montie JE
FAU - Chinnaiyan, Arul M
AU  - Chinnaiyan AM
FAU - Shah, Rajal B
AU  - Shah RB
LA  - eng
GR  - P50 CA69568/CA/NCI NIH HHS/United States
GR  - PC040517/PC/NCI NIH HHS/United States
GR  - U01 CA111275-01/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.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.- (TMPRSS2 protein, human)
SB  - IM
MH  - Adenocarcinoma/*genetics/pathology
MH  - Gene Deletion
MH  - *Genetic Heterogeneity
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Models, Biological
MH  - Neoplasms, Multiple Primary/*genetics/pathology
MH  - Prostatic Neoplasms/*genetics/pathology
MH  - Serine Endopeptidases/*genetics
MH  - *Translocation, Genetic
EDAT- 2007/09/07 09:00
MHDA- 2007/10/31 09:00
CRDT- 2007/09/07 09:00
PHST- 2007/09/07 09:00 [pubmed]
PHST- 2007/10/31 09:00 [medline]
PHST- 2007/09/07 09:00 [entrez]
AID - 67/17/7991 [pii]
AID - 10.1158/0008-5472.CAN-07-2043 [doi]
PST - ppublish
SO  - Cancer Res. 2007 Sep 1;67(17):7991-5. doi: 10.1158/0008-5472.CAN-07-2043.