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High Resolution Characterization of a Common Genetic Alteration in Prostrate Cancer
A review of TMPRSS2 Fusions with Oncogenic ETS Factors in Prostate Cancer Involve Unbalanced Genomic Rearrangements and Are Associated with HDAC1 and Epigenetic Reprogramming
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
Up to half of all prostrate cancers contain a translocation of TMPRSS2, which results in the fusion of the strong androgen-responsive gene to oncogenic ETS factors such as ERG, ETV1, or ETV4. Iljin and colleagues (2006) studied 18 advanced prostrate cancers for ETS factor alterations, and then explored tumors with high ERG expression using Agilent’s Human Genome CGH 44A and 44B oligo microarrays to reveal associated chromosomal aberrations. Using Agilent’s aCGH arrays, the group characterized genomic rearrangements (deletions at the ERG locus or interstitial deletions between the TMPRSS2 and ERG loci), in five out of the six samples displaying TMPRSS2:ERG gene fusions with high ERG expression. These results indicate that ERG activation is not caused by simple balanced translocation, but by a variety of unbalanced genetic rearrangements that bring together these two adjacent loci. In one of the tumors, there were two microdeletions both at the TMPRSS2 and ERG loci (measuring 911 and 159 kb, respectively), suggesting that complex genetic rearrangements led to fusion gene formation. The results of this study shed new light into the mechanism of disease in ERG-positive prostate cancers by discovering that ERG may contribute, directly or indirectly, to several different phenotypic hallmarks of cancer.
Figure 1. Array-based CGH data showing deletions between ERG and TMPRSS2 in advanced prostate cancers and metastases.
Chromosome 21 copy number profiles at ERG/TMPRSS2 region at q22.2-q22.3 from specimens with a reduction of copy number. In sample no. 10, only a modest indication of copy number reduction was detected, whereas in sample no. 18, the actual breakpoint occurred proximally from ERG. Examples from cases with interstitial deletion (sample no. 14) and smaller microdeletions affecting ERG and TMPRSS2 loci (sample no. 4) are also shown.
Title: TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming.
Authors: Iljin K, Wolf M, Edgren H, Gupta S, Kilpinen S, Skotheim RI, Peltola M, Smit F, Verhaegh G, Schalken J, Nees M, Kallioniemi O.
Journal: Cancer Res. 2006 Nov 1;66(21):10242-6.
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