Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer.
BACKGROUND
The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer.


METHODS
In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127).


RESULTS
Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22-3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03).


CONCLUSIONS
If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.
FitzGerald
Liesel M
LM
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA 98109, USA. lfitzger@fhcrc.org
Agalliu
Ilir
I
Johnson
Karynn
K
Miller
Melinda A
MA
Kwon
Erika M
EM
Hurtado-Coll
Antonio
A
Fazli
Ladan
L
Rajput
Ashish B
AB
Gleave
Martin E
ME
Cox
Michael E
ME
Ostrander
Elaine A
EA
Stanford
Janet L
JL
Huntsman
David G
DG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human