This graphical abstract shows the two ways the TMPRESS2-ERG fusion mutation can occur.

The TMPRSS2-ERG mutation is one of the most common mutations that occur in prostate cancer. This mutation relies on two separate genes, TMPRSS2 and ERG. The TMPRS22 gene codes for a transmembrane protease that is expressed in the cell lining of the prostate gland (Adamo et al.). In the prostate, this protein activates the protease-activated receptor-2. Through this activation, a signal transduction pathway associated with TMPRSS2 can influence inflammation, metastasis, and invasion of foreign pathogens in the prostate gland. While the TIMPRSS2 gene and protein serve many important functions, the ERG gene and Erg protein does as well.

The ETS-related gene or ERG is a member of the E-26 transformation specific family of transcription factors. This family of transcription factors has roles in development. The developments that ERG is responsible for range from the vascular system, blood cells and platelets, and bones. It has been well documented has played roles in other types of cancer such as sarcoma and leukemia. Within the last decade, researchers have been able to expand their knowledge about ERG and was able to connect it to other cancers such as prostate cancer. Since ERG and TMPRSS2 play a role in prostate cancer, it is important to understand how the mutation occurred that got these two genes fused.

While both genes are important for regular function, it is also important to understand how they become dysfunctional. The TMPRSS2-ERG fusion occurs because a DNA rearrangement event. This event shows that the first exon of TMPRESS2 is connected to the fourth exon of ERG (Tomlins et al.). Alternatively, a deletion on chromosome 21 can occur. Specifically, the deletion of 21q22.2-3 leads to the fusion of TMPRESS2-ERG fusion gene (Perner et al.). Once the mechanism for how the mutation occurs was understood, researchers moved onto understanding the roles of the mutation in prostate cancer.

Understanding the extent of the TMPRSS2-ERG fusion mutation is a multifaceted problem. Cerveira et al. looked at lesions in prostate cancer cells. These lesions are often looked at in pathology reports to help diagnose prostate cancer. Additionally, Cervia et al. identified that the majority of the prostate cancer cells that present with these lesions also have the TMPRSS2-ERG fusion mutation. This helps tie together the effects of the mutation and the pathology of the disease.

In addition to the pathology of the disease, scientists needed to understand how the TMPRSS2-ERG fusion mutation impacts the levels of PSA since PSA is a common diagnostic tool. Herman et al. validates that the mechanism that causes the mutation is correct in previous literature. Additionally, this group examined the connection between new cancers with the TMPRSS2-ERG fusion mutation and whether they are androgen dependent. Androgen, a class of sex hormones similar to testosterone, is in fluctuation when a patient has prostate cancer. The group found that the majority of new prostate cancers also have an upregulated expression of androgen. This upregulation is significant because androgen plays a role in the regulation of the fusion mutation and the regulation of the mutation is important since it can control the severity of the prostate cancer. While the scientific community knows a lot about this mutation, there are still aspects of the mutation that are not known about the mutation. To progress further and learning how to control and treat prostate cancer with the TMPRSS2-ERG fusion gene mutation, scientist will have to understand this mutation and continue to make connections between pathology, diagnoses, treatment, and prevention.

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