Related Experiment Video
Updated: Jun 21, 2026
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
ETS gene fusions in prostate cancer
Jeremy P Clark1, Colin S Cooper
1Male Urological Cancer Research Centre, Sutton, UK. jeremy.clark@icr.ac.uk
Abstract:
Chromosomal rearrangements that result in high level expression of ETS gene family members are common events in human prostate cancer. Most frequently, the androgen-activated gene TMPRSS2 is found fused to the ERG gene. Fusions involving ETV1, ETV4 and ETV5 occur less frequently but exhibit greater variability in fusion structure with 12 unique 5' fusion partners identified so far. ETS gene rearrangement seems to be a key event in driving prostate neoplastic development: the rearrangement occurs as an early event and continues to be expressed in metastatic and castration-resistant disease. However, ETS alterations seem insufficient on their own to induce cancer formation. No consistent associations are seen between the presence of ETS alteration and clinical outcome, with the possible exception that duplication of rearranged ERG, reflecting aneuploidy, is associated with poor outcome. Thus, factors other than ERG gene status may be the major determinants of poor clinical outcome. Expression signatures of prostate cancers containing the TMPRSS2-ERG fusion suggest involvement of beta-estradiol signaling, and reveal higher levels of expression of HDAC1 and ion channel genes when compared to cancers that lack the rearrangement. These observations suggest new therapeutic possibilities for patients harboring ETS gene fusions.
Insights
ETS gene rearrangements are early events in prostate cancer, driving neoplastic development. While not sufficient alone, they suggest therapeutic targets, particularly TMPRSS2-ERG fusions.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Chromosomal rearrangements activating ETS gene family members are frequent in prostate cancer.
- TMPRSS2-ERG gene fusions are the most common, while ETV1, ETV4, and ETV5 fusions are less frequent but more varied.
- ETS gene rearrangements are early events in prostate cancer development, persisting through metastatic and castration-resistant stages.
Purpose of the Study:
- To investigate the role of ETS gene rearrangements in prostate cancer.
- To explore the association between ETS alterations and clinical outcomes.
- To identify potential therapeutic strategies based on ETS gene fusion expression signatures.
Main Methods:
- Analysis of ETS gene family member expression in prostate cancer.
- Identification and characterization of gene fusion structures.
- Comparison of gene expression profiles between cancers with and without ETS rearrangements.
Main Results:
- ETS gene rearrangements are early events in prostate cancer and are present in advanced disease stages.
- ETS alterations alone are insufficient for cancer induction; only ERG duplication correlates with poor outcome.
- Prostate cancers with TMPRSS2-ERG fusions show distinct expression signatures, including beta-estradiol signaling and higher HDAC1 and ion channel gene expression.
Conclusions:
- ETS gene rearrangements are critical early events in prostate cancer pathogenesis.
- Clinical outcome is not solely determined by ETS gene status, suggesting other factors are involved.
- Expression patterns associated with ETS fusions, like TMPRSS2-ERG, offer potential therapeutic avenues.
Related Concept Videos
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
02:11Reporter Genes
Commonly used reporter...
00:59Gene Therapy
02:38The Ras Gene
Ras is a superfamily...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...