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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.

Speckle-type POZ protein mutations in prostate cancer: a new part of the mosaic