A. The 374 amino acid SPOP protein consists of an N-terminal meprin and TRAF-homology (MATH) domain, a BTB substrate binding, otherwise known as a pox virus and zinc finger (POZ), domain, and a C-terminal nuclear localization sequence. The SPOP N296I mutation resides in the Bric-a-brac, Tramtrack, Broad-complex (BTB) binding domain. The somatic mutations identified in prostate tumors are located in the MATH domain. B) Chromatograms showing the presence of the N296I missense mutation in both germline and tumor DNA from our index case.