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| INVITED COMMENTARY |
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| Year : 2015 | Volume
: 17
| Issue : 1 | Page : 161 |
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Speckle-type POZ protein mutations in prostate cancer: a new part of the mosaic
Robert Stoehr
Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| Date of Web Publication | 14-Oct-2014 |
Correspondence Address:
Robert Stoehr
Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen
Germany
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1008-682X.140965
How to cite this article:
Stoehr R. Speckle-type POZ protein mutations in prostate cancer: a new part of the mosaic. Asian J Androl 2015;17:161 |
Prostate cancer (PCa) is still the leading cause of death among males worldwide and an enormous burden for the healthcare systems. Therefore, huge efforts were made to understand the molecular basis of PCa and to reveal biomarkers for predicting the clinical course of the disease. The advent of new and highly efficient sequencing technologies (e.g. next-generation sequencing [NGS]) allowed the analysis of whole tumor cell genomes and brought deep insights into molecular alterations of these cells. Using these tools, the search for molecular biomarkers will progress rapidly.
In PCa, NGS studies revealed the speckle-type POZ protein (SPOP) as one of the most frequently mutated genes reported so far recently. The average rate of SPOP mutation was about 10% in primary and metastatic tumors, and these mutations were suggested to be an early event in prostate carcinogenesis. [1] Interestingly, wild-type SPOP degrades full-length androgen receptor (AR) and possesses functions of a tumor-suppressor. Mutated SPOP is no longer capable of this AR degradation and was supposed to be involved in the resistance of an anti-androgen-therapy of PCa. [2]
Most of these data on SPOP mutations came from studies on Caucasian patient cohorts only. As the published studies hypothesize a general role of SPOP alterations in PCa analysis of patients from diverse ethnicity is urgently needed. Buckles et al. [3] present a comprehensive study of SPOP mutation analysis in African American PCa patients (n = 49). Although, only a relatively small number of patients analyzed SPOP mutations were found in 10% of the cases. Most recently, a very similar study was published by Khani et al. [4] Herein, a mutation frequency of only 4.5% (n = 4/88) was reported with an overlapping mutation spectrum between both studies. As Khani et al. [4] isolated tumor DNA from tissue cores detection of SPOP mutations might have been hampered by the presence of a lot of nonneoplastic cells within the cores. As Buckles et al. [3] used macro dissection before DNA isolation a high purity of the tumor cells could be expected. Nevertheless, Khani et al. [4] found no significant difference in the SPOP mutation frequency between Caucasian and African American PCa patients. Both reports underline the general importance of SPOP mutation in PCa. In addition, Buckles et al. [3] also found a decreased SPOP expression on mRNA level in mutated tumors. Unfortunately, SPOP expression analysis on protein level was not done on the tumor tissue. Kim et al. [5] showed that more than 35% (n = 22/60) of the analyzed PCa cases lost SPOP expression using immunohistochemistry, but only two cases with SPOP mutation were analyzed in parallel for mutation and expression. It will be of great interest if somatic mutations are the cause of the expression loss or if other mechanisms (e.g. epigenetic, posttranscriptional or posttranslational modification) are involved in SPOP protein loss.
Remarkably, Buckles et al. [3] could also report a significant correlation between the presence of SPOP mutation and aggressive PCa. As a correlation between SPOP mutations and histopathological characteristics of the tumors was not found to date, validation of this clinical important impact of SPOP mutation on PCa is urgently needed.
Taken together, the reported studies on the role of SPOP alterations in PCa provide a promising new, and presumably large tesserae of the overall picture of PCa that hopefully improve management of this disease in the future.
Competing Interests
The authors declare that they have no competing interests.
| References | |  |
| 1. | Mani RS. The emerging role of speckle-type POZ protein (SPOP) in cancer development. Drug Discov Today 2014; 19: 1498-1502.  |
| 2. | An J, Wang C, Deng Y, Yu L, Huang H. Destruction of full-length androgen receptor by wild-type SPOP, but not prostate-cancer-associated mutants. Cell Rep 2014; 6: 657-69. |
| 3. | Buckles E, Qian C, Tadros A, Majumdar S, Cvitanovic J, et al. Identification of speckle-type POZ protein somatic mutations in African American prostate cancer. Asian J Androl 2014; 16: 829-32. |
| 4. | Khani F, Mosquera JM, Park K, Blattner M, O'Reilly C, et al. Evidence for molecular differences in prostate cancer between African American and Caucasian men. Clin Cancer Res 2014; 20: 4925-34. |
| 5. | Kim MS, Je EM, Oh JE, Yoo NJ, Lee SH. Mutational and expressional analyses of SPOP, a candidate tumor suppressor gene, in prostate, gastric and colorectal cancers. APMIS 2013; 121: 626-33. |
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