PMID- 23794398
OWN - NLM
STAT- MEDLINE
DCOM- 20131018
LR  - 20220330
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Linking)
VI  - 231
IP  - 1
DP  - 2013 Sep
TI  - Recurrent deletion of 3p13 targets multiple tumour suppressor genes and defines a 
      distinct subgroup of aggressive ERG fusion-positive prostate cancers.
PG  - 130-41
LID - 10.1002/path.4223 [doi]
AB  - Deletion of 3p13 has been reported from about 20% of prostate cancers. The 
      clinical significance of this alteration and the tumour suppressor gene(s) 
      driving the deletion remain to be identified. We have mapped the 3p13 deletion 
      locus using SNP array analysis and performed fluorescence in situ hybridization 
      (FISH) analysis to search for associations between 3p13 deletion, prostate cancer 
      phenotype and patient prognosis in a tissue microarray containing more than 3200 
      prostate cancers. SNP array analysis of 72 prostate cancers revealed a small 
      deletion at 3p13 in 14 (19%) of the tumours, including the putative tumour 
      suppressors FOXP1, RYBP and SHQ1. FISH analysis using FOXP1-specific probes 
      revealed deletions in 16.5% and translocations in 1.2% of 1828 interpretable 
      cancers. 3p13 deletions were linked to adverse features of prostate cancer, 
      including advanced stage (p < 0.0001), high Gleason grade (p = 0.0125), and early 
      PSA recurrence (p = 0.0015). In addition, 3p13 deletions were linked to ERG(+) 
      cancers and to PTEN deletions (p < 0.0001 each). A subset analysis of ERG(+) 
      tumours revealed that 3p13 deletions occurred independently from PTEN deletions 
      (p = 0.3126), identifying tumours with 3p13 deletion as a distinct molecular 
      subset of ERG(+) cancers. mRNA expression analysis confirmed that all 3p13 genes 
      were down regulated by the deletion. Ectopic over-expression of FOXP1, RYBP and 
      SHQ1 resulted in decreased colony-formation capabilities, corroborating a tumour 
      suppressor function for all three genes. In summary, our data show that deletion 
      of 3p13 defines a distinct and aggressive molecular subset of ERG(+) prostate 
      cancers, which is possibly driven by inactivation of multiple tumour suppressors.
CI  - Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Krohn, Antje
AU  - Krohn A
AD  - Institute of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Seidel, Annemarie
AU  - Seidel A
FAU - Burkhardt, Lia
AU  - Burkhardt L
FAU - Bachmann, Frederic
AU  - Bachmann F
FAU - Mader, Malte
AU  - Mader M
FAU - Grupp, Katharina
AU  - Grupp K
FAU - Eichenauer, Till
AU  - Eichenauer T
FAU - Becker, Andreas
AU  - Becker A
FAU - Adam, Meike
AU  - Adam M
FAU - Graefen, Markus
AU  - Graefen M
FAU - Huland, Hartwig
AU  - Huland H
FAU - Kurtz, Stefan
AU  - Kurtz S
FAU - Steurer, Stefan
AU  - Steurer S
FAU - Tsourlakis, Maria C
AU  - Tsourlakis MC
FAU - Minner, Sarah
AU  - Minner S
FAU - Michl, Uwe
AU  - Michl U
FAU - Schlomm, Thorsten
AU  - Schlomm T
FAU - Sauter, Guido
AU  - Sauter G
FAU - Simon, Ronald
AU  - Simon R
FAU - Sirma, Huseyin
AU  - Sirma H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (FOXP1 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Repressor Proteins)
RN  - 0 (TMPRSS2-ERG fusion protein, human)
SB  - IM
MH  - Adenocarcinoma/*genetics/metabolism/mortality/pathology
MH  - Cell Line, Tumor
MH  - *Chromosome Deletion
MH  - Chromosomes, Human, Pair 3/*genetics
MH  - Forkhead Transcription Factors/genetics/metabolism
MH  - Gene Expression Profiling
MH  - Gene Knockdown Techniques
MH  - *Genes, Tumor Suppressor
MH  - Germany/epidemiology
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Neoplasm Recurrence, Local
MH  - Oligonucleotide Array Sequence Analysis
MH  - Oncogene Proteins, Fusion/metabolism
MH  - Polymorphism, Single Nucleotide
MH  - Prostate/metabolism/pathology
MH  - Prostatectomy
MH  - Prostatic Neoplasms/*genetics/metabolism/mortality/pathology
MH  - Repressor Proteins/genetics/metabolism
MH  - Tissue Array Analysis
OTO - NOTNLM
OT  - 3p13 deletion
OT  - ERG
OT  - FOXP1
OT  - PTEN
OT  - RYBP
OT  - SHQ1
OT  - prostate cancer
EDAT- 2013/06/25 06:00
MHDA- 2013/10/19 06:00
CRDT- 2013/06/25 06:00
PHST- 2012/08/07 00:00 [received]
PHST- 2013/05/03 00:00 [revised]
PHST- 2013/05/27 00:00 [accepted]
PHST- 2013/06/25 06:00 [entrez]
PHST- 2013/06/25 06:00 [pubmed]
PHST- 2013/10/19 06:00 [medline]
AID - 10.1002/path.4223 [doi]
PST - ppublish
SO  - J Pathol. 2013 Sep;231(1):130-41. doi: 10.1002/path.4223.