By searching through the literature, I was able to focus my topic to the TMPRSS2-ERG mutation in prostate cancer. I will start the review by giving a general introduction to cancer and specifically explain prostate cancer. From the introduction, I will talk about prostate specific antigen since it gives some background information and can be tied into the pathology of the disease. Once this foundation is laid I will go into detail about the mutation itself. Since the mutation interacts with the PI3K pathway, I will explain that pathway and what implications are present since it is activated by downstream dysregulation. After talking about this pathway, I will talk about the proposed mechanism of the disease through a growth and metabolism lens. Since these biochemical mechanisms are new (the first biochemical based metabolism mechanism was proposed just two years ago) I will talk about where the field is heading.
The Six Big Themes:
In the introduction I will quickly explain the general basics of cancer. Once these are explained I will talk about the different types of cancer and what can influence carcinogenesis. There are population studies that are published that give information about how many people get each type of cancer and how many people die from the caner (Ferlay et al. 2015). Also, there are studies explain the genetic difference between tumor cells which is important to cover since I will only be talking about one specific mutation that leads to cancer (“The Molecular Taxonomy of Primary Prostate Cancer” 2015). Lastly, I will introduce prostate specific antigen (PSA) since it also has some background information.
Since PSA is used for diagnosis and revolutionized the field of prostate cancer diagnosis, I am going to briefly talk about it. Additionally, there have been some recent studies that tie PSA levels with the pathology of the disease (Demichelis et al. 2007). I will use this connection to talk about the TMPRSS2-ERG mutation.
- TMPRSS2-ERG mutation “First Wave”:
The majority of the review will be spent on this section. This is because the large majority of the research published in the last decade has been focused on understanding this mutation and in addition to this, this mutation is complex, and features deletions and fusions. I will talk about the role of each of these proteins when they are not mutated and how they got mutated. Finally, I will wrap this section up the implications of the mutations which will lead me to the PI3K pathway.
- 4. PI3K Pathway “Second Wave”:
This section of the review will be the second biggest since this is can be thought as the big second wave of research that was done to understand the etiology of prostate cancers with the TMPRSS2-ERG mutation. The PI3K pathway features a connection to other proto-oncogenes and cell division pathways. Through this connection, we will see that it is still not crystal clear how all these pathways interact to promote carcinogenesis of prostate cancer.
- Disease Mechanism “Third Wave”:
This section will be relatively short because not a lot of research has hit this point yet. With this being said, this will probably be the most interesting part of the review for the BCM441 class because it starts to talk about how the cancer impacts the metabolism of surrounding tissues. The metabolism of fatty acids for instance is impacted by the cancer which leads to various problems in the cell that allow for the cancer cell to create a niche for rapid growth and division.
- Future Work:
In the final section of the review I will talk about where the field is going as a whole. As previously stated, we are still on “Wave 2/3”. With this being said, we can see that the field is going towards understanding the pathways, seeing how these pathways interfere with cellular processes such as metabolism, and finally see how the dysregulation of ETS interferes with various unknown cellular processes to promote carcinogenesis.
Demichelis, F., K. Fall, S. Perner, O. Andrén, F. Schmidt, S. R. Setlur, Y. Hoshida, et al. 2007. “TMPRSS2:ERG Gene Fusion Associated with Lethal Prostate Cancer in a Watchful Waiting Cohort.” Oncogene 26 (31): 4596–99. https://doi.org/10.1038/sj.onc.1210237.
Ferlay, Jacques, Isabelle Soerjomataram, Rajesh Dikshit, Sultan Eser, Colin Mathers, Marise Rebelo, Donald Maxwell Parkin, David Forman, and Freddie Bray. 2015. “Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012.” International Journal of Cancer 136 (5): E359–86. https://doi.org/10.1002/ijc.29210.
“The Molecular Taxonomy of Primary Prostate Cancer.” 2015. Cell 163 (4): 1011–25. https://doi.org/10.1016/j.cell.2015.10.025.