G3BP1 and Familial prostate cancer: While somatic SPOP mutations at the substrate-binding MATH domain are primarily prostate cancer-specific, G3BP1 overexpression (G3BP1high) is a much broader oncogenic signature in a wide spectrum of tumor types25,26,50, suggesting that suppression of SPOP by G3BP1 is likely more prevalent (20% high and 40% moderate) and is the underlying mechanism of SPOP inactivation in other tumor types.