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. Author manuscript; available in PMC: 2014 Aug 29.
Published in final edited form as: Cell. 2013 Aug 29;154(5):1074–1084. doi: 10.1016/j.cell.2013.07.029

Fig. 2.

Fig. 2

Somatic selection for HSD3B1(1245C) encoding 3βHSD1(367T) occurs with resistance to androgen deprivation. (A) Conversion from A → C in HSD3B1 occurs in 3 CRPC tumors from patients with homozygous wild-type inheritance. Sequence of cDNA clones from a fresh-frozen tumor (UTSW7) confirms expression of HSD3B1(1245C) transcript. (B) Three CRPC tumors from patients with heterozygous inheritance exhibit LOH of the wild-type HSD3B1(1245A) allele. Sequencing informative (heterozygous) adjacent 5’ (rs6203) and 3’ (rs34814922 and rs113096733) SNPs confirms LOH. (C) 3βHSD1 protein is abundant in tumors with LOH of the HSD3B1(1245A) allele but not tumors with heterozygous expression or homozygous HSD3B1(1245A) expression. Both tumors with LOH tested also express AR and PSA (20 μg protein loaded per lane for each tumor). (D) Somatic mutation converting A → C in HSD3B1 occurs in two LAPC4 xenograft tumors treated with abiraterone acetate (Abi) after orchiectomy and expression of HSD3B1(1245C) transcript encoding 3βHSD1(367T) is evidenced by sequencing cDNA clones from these tumors. Genomic sequence from two representative control tumors (CTRL#1 and CTRL#2) treated with orchiectomy alone is shown for comparison. All 37 cDNA clones from CTRL#1 and CTRL#2 have HSD3B1(1245A) transcript encoding 3βHSD1(367N). See also Figure S2 and Table S1.