Document Detail


Recurrent rearrangements in prostate cancer: causes and therapeutic potential.
MedLine Citation:
PMID:  23410129     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DNA damage and genetic rearrangements are hallmarks of cancer. However, gene fusions as driver mutations in cancer have classically been a distinction in leukemia and other rare instances until recently with the discovery of gene fusion events occurring in 50 to 75% of prostate cancer patients. The discovery of the TMPRSS2-ERG fusion sparked an onslaught of discovery and innovation resulting in a delineation of prostate cancer via a molecular signature of gene fusion events. The increased commonality of high-throughput sequencing data coupled with improved bioinformatics approaches not only elucidated the molecular underpinnings of prostate cancer progression, but the mechanisms of gene fusion biogenesis. Interestingly, the androgen receptor (AR), already known to play a significant role in prostate cancer tumorigenesis, has recently been implicated in the processes resulting in gene fusions by inducing the spatial proximity of genes involved in rearrangements, promoting the formation of double-strand DNA breaks (DSB), and facilitating the recruitment of proteins for non-homologous end-joining (NHEJ). Our increased understanding of the mechanisms inducing genomic instability may lead to improved diagnostic and therapeutic strategies. To date, the majority of prostate cancer patients can be molecularly stratified based on their gene fusion status thereby increasing the potential for tailoring more specific and effective therapies.
Authors:
Nicole M White; Felix Y Feng; Christopher A Maher
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current drug targets     Volume:  14     ISSN:  1873-5592     ISO Abbreviation:  Curr Drug Targets     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-09     Completed Date:  2014-01-30     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  100960531     Medline TA:  Curr Drug Targets     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  450-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
DNA Breaks, Double-Stranded
Gene Fusion
Gene Rearrangement*
Humans
Male
Oncogene Proteins, Fusion / genetics,  metabolism
Prostatic Neoplasms / genetics*,  pathology*
Receptors, Androgen / genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
R00 CA149182/CA/NCI NIH HHS; R00 CA149182/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Oncogene Proteins, Fusion; 0/Receptors, Androgen
Comments/Corrections

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