Table 1.
Somatic mutations in steroidogenic genes in clinical PCa tissues. COSMIC and cBIO databases were queried for somatic mutations in genes that encode protein involved in the synthesis, metabolism, and transport of androgens [28]. The COSMIC database was queried via the Cancer browser, selecting for “prostate cancer” and “carcinoma” histology, and retrieving only data from genome-wide sequencing efforts. For cBIO analysis, datasets analyses are marked by first author of study that was examined.
| Genes | COSMIC |
cBIO |
||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| # | ADT-naïve | ADT-naïve | ADT-naïve | ADT-naïve | ADT-naïve | + CRPC | CRPC | CRPC | ADT-naïve | CRPC | ||||||
| n=1 976 | Barbieri | n=112 | Fraser | n=477 | TCGA | n=333 | Armenia | n=1 013 | Abida | n=444 | Beltran | n=114 | n=922 | n=558 | ||
| % | # | % | # | % | # | % | # | % | # | % | # | % | average% | average% | ||
| ABCG5 | 9 | 0.46 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 5 | 0.49 | 6 | 1.35 | 1 | 0.88 | 0.00 | 1.11 |
| ABCG8 | 5 | 0.25 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 5 | 0.49 | 4 | 0.90 | 0 | 0.00 | 0.10 | 0.45 |
| AKR1C1 | 5 | 0.25 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 3 | 0.30 | 1 | 0.23 | 0 | 0.00 | 0.10 | 0.11 |
| AKR1C2 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 1 | 0.10 | 2 | 0.45 | 0 | 0.00 | 0.00 | 0.23 |
| AKR1C3 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 3 | 0.30 | 1 | 0.23 | 1 | 0.88 | 0.00 | 0.55 |
| AKR1C4 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 3 | 0.30 | 2 | 0.45 | 1 | 0.88 | 0.00 | 0.66 |
| CYP11A1 | 8 | 0.40 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 2 | 0.20 | 1 | 0.23 | 0 | 0.00 | 0.00 | 0.11 |
| CYP11B1 | 8 | 0.40 | 1 | 0.89 | 0 | 0.00 | 0 | 0.00 | 10 | 0.99 | 8 | 1.80 | 2 | 1.75 | 0.30 | 1.78 |
| CYP11B2 | 7 | 0.35 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 8 | 0.79 | 6 | 1.35 | 0 | 0.00 | 0.10 | 0.68 |
| CYP17A1 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 2 | 0.20 | 1 | 0.23 | 0 | 0.00 | 0.00 | 0.11 |
| CYP19A1 | 7 | 0.35 | 0 | 0.00 | 2 | 0.42 | 1 | 0.30 | 3 | 0.30 | 1 | 0.23 | 0 | 0.00 | 0.24 | 0.11 |
| CYP1A1 | 5 | 0.25 | 1 | 0.89 | 0 | 0.00 | 1 | 0.30 | 5 | 0.49 | 2 | 0.45 | 1 | 0.88 | 0.40 | 0.66 |
| CYP1B1 | 4 | 0.20 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 3 | 0.30 | 4 | 0.90 | 0 | 0.00 | 0.00 | 0.45 |
| CYP21A2 | 8 | 0.40 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 3 | 0.30 | 2 | 0.45 | 0 | 0.00 | 0.10 | 0.23 |
| CYP3A4 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 3 | 0.30 | 1 | 0.23 | 0 | 0.00 | 0.00 | 0.11 |
| CYP3A43 | 2 | 0.10 | 0 | 0.00 | 0 | 0.00 | 2 | 0.60 | 3 | 0.30 | 2 | 0.45 | 0 | 0.00 | 0.20 | 0.23 |
| CYP3A5 | 2 | 0.10 | 1 | 0.89 | 1 | 0.21 | 0 | 0.00 | 4 | 0.39 | 1 | 0.23 | 1 | 0.88 | 0.37 | 0.55 |
| CYP3A7 | 3 | 0.15 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 2 | 0.20 | 1 | 0.23 | 0 | 0.00 | 0.00 | 0.11 |
| HSD17B1 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 1 | 0.10 | 0 | 0.00 | 1 | 0.88 | 0.00 | 0.44 |
| HSD17B10 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0.00 | 0.00 |
| HSD17B11 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 2 | 0.60 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0.20 | 0.00 |
| HSD17B12 | 2 | 0.10 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0.00 | 0.00 |
| HSD17B13 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0.00 | 0.00 |
| HSD17B14 | 2 | 0.10 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 2 | 0.20 | 2 | 0.45 | 1 | 0.88 | 0.00 | 0.66 |
| HSD17B2 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 3 | 0.30 | 3 | 0.68 | 0 | 0.00 | 0.00 | 0.34 |
| HSD17B3 | 14 | 0.71 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 4 | 0.39 | 2 | 0.45 | 0 | 0.00 | 0.00 | 0.23 |
| HSD17B4 | 4 | 0.20 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 5 | 0.49 | 3 | 0.68 | 0 | 0.00 | 0.10 | 0.34 |
| HSD17B6 | 2 | 0.10 | 0 | 0.00 | 1 | 0.21 | 0 | 0.00 | 2 | 0.20 | 1 | 0.23 | 1 | 0.88 | 0.07 | 0.55 |
| HSD17B7 | 2 | 0.10 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 1 | 0.23 | 0 | 0.00 | 0.00 | 0.11 |
| HSD17B8 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 1 | 0.10 | 0 | 0.00 | 0 | 0.00 | 0.00 | 0.00 |
| HSD3B1 | 5 | 0.25 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 2 | 0.20 | 0 | 0.00 | 0 | 0.00 | 0.10 | 0.00 |
| HSD3B2 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 3 | 0.30 | 1 | 0.23 | 0 | 0.00 | 0.10 | 0.11 |
| HSD3B7 | 6 | 0.30 | 1 | 0.89 | 0 | 0.00 | 0 | 0.00 | 4 | 0.39 | 2 | 0.45 | 0 | 0.00 | 0.30 | 0.23 |
| RDH15 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 1 | 0.10 | 1 | 0.23 | 0 | 0.00 | 0.00 | 0.11 |
| RDH16 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 3 | 0.30 | 2 | 0.45 | 0 | 0.00 | 0.00 | 0.23 |
| RDH5 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0.00 | 0.00 |
| SHBG | 2 | 0.10 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 1 | 0.10 | 1 | 0.23 | 0 | 0.00 | 0.10 | 0.11 |
| SLCO1A2 | 5 | 0.25 | 0 | 0.00 | 1 | 0.21 | 0 | 0.00 | 6 | 0.59 | 2 | 0.45 | 0 | 0.00 | 0.07 | 0.23 |
| SLCO1B1 | 6 | 0.30 | 0 | 0.00 | 1 | 0.21 | 1 | 0.30 | 4 | 0.39 | 0 | 0.00 | 0 | 0.00 | 0.17 | 0.00 |
| SLCO1B3 | 5 | 0.25 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 2 | 0.20 | 1 | 0.23 | 0 | 0.00 | 0.00 | 0.11 |
| SLCO1C1 | 5 | 0.25 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 4 | 0.39 | 1 | 0.23 | 0 | 0.00 | 0.10 | 0.11 |
| SLCO2A1 | 5 | 0.25 | 1 | 0.89 | 0 | 0.00 | 1 | 0.30 | 4 | 0.39 | 5 | 1.13 | 0 | 0.00 | 0.40 | 0.56 |
| SLCO2B1 | 7 | 0.35 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 8 | 0.79 | 3 | 0.68 | 6 | 5.26 | 0.10 | 2.97 |
| SLCO3A1 | 18 | 0.91 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 9 | 0.89 | 3 | 0.68 | 1 | 0.88 | 0.00 | 0.78 |
| SLCO4A1 | 9 | 0.46 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 5 | 0.49 | 3 | 0.68 | 2 | 1.75 | 0.00 | 1.22 |
| SLCO4C1 | 8 | 0.40 | 4 | 3.57 | 1 | 0.21 | 0 | 0.00 | 12 | 1.18 | 5 | 1.13 | 0 | 0.00 | 1.26 | 0.56 |
| SLCO5A1 | 11 | 0.56 | 0 | 0.00 | 0 | 0.00 | 1 | 0.30 | 5 | 0.49 | 5 | 1.13 | 0 | 0.00 | 0.10 | 0.56 |
| SLCO6A1 | 12 | 0.61 | 1 | 0.89 | 0 | 0.00 | 1 | 0.30 | 14 | 1.38 | 9 | 2.03 | 0 | 0.00 | 0.40 | 1.01 |
| SRD5A1 | 1 | 0.05 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0.00 | 0.00 |
| SRD5A2 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 0.00 | 0.00 |
| SRD5A3 | 3 | 0.15 | 0 | 0.00 | 1 | 0.21 | 0 | 0.00 | 3 | 0.30 | 3 | 0.68 | 0 | 0.00 | 0.07 | 0.34 |
| STAR | 3 | 0.15 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 2 | 0.20 | 2 | 0.45 | 1 | 0.88 | 0.00 | 0.66 |
| UGT2B15 | 2 | 0.10 | 0 | 0.00 | 0 | 0.00 | 3 | 0.90 | 3 | 0.30 | 0 | 0.00 | 0 | 0.00 | 0.30 | 0.00 |
| UGT2B17 | 3 | 0.15 | 0 | 0.00 | 0 | 0.00 | 0 | 0.00 | 4 | 0.39 | 0 | 0.00 | 0 | 0.00 | 0.00 | 0.00 |
| UGT2B7 | 2 | 0.10 | 0 | 0.00 | 2 | 0.42 | 1 | 0.30 | 7 | 0.69 | 1 | 0.23 | 1 | 0.88 | 0.24 | 0.55 |
Corresponding cBIO annotations is as follows: Barbieri, Prostate Adenocarcinoma (Broad/Cornell, Nature Genetics 2012); Fraser, Prostate Adenocarcinoma (CPC-Gene, Nature 2017); Armenia, Prostate Adenocarcinoma (MSKCC/DFCI, Nature Genetics 2018); Abida, Metastatic Prostate Adenocarcimoma, SU2C/PCF Dream Team, PNAS 2019; Beltran, Neuroendocrine Prostate Cancer (Multi-institute, Nature Medicine 2016). Note that the Armenia et al. study includes data from 680 ADT-naïve and 333 CRPC cases; data from this study have not been taken into consideration in determining average %.
#, number of somatic mutations/study that affect the gene for which the symbol is listed.
%, percentage of cases/study that harbor somatic mutations that affect the gene for which the symbol is listed.
Average %, average of percentage of mutations from studies on either ADT-naïve PCa or CRPC specimens; ADT, androgen deprivation therapy; CRPC, castration-resistant PCa; PCa, prostate cancer.