TABLE 3.
Recurrent genomic alterations in lung-only mHSPC cases compared to men with sporadic localized and castration-resistant prostate cancer
| Lung-only |
TCGAa |
SU2Cb |
|||||
|---|---|---|---|---|---|---|---|
| N = 16 |
N = 333 |
N = 150 |
Lung-only vs TCGA |
Lung-only vs SU2C |
|||
| Gene/pathway | No. of mutations (% of men) | RR (95% CI) | P value | RR (95% CI) | P value | ||
| Any DDR alteration | 10 (63) | 62 (19) | 34 (23) | 3.36 (2.16-5.22) | <.001 | 2.76 (1.70-4.46) | <.001 |
| Any MMR alteration | 4 (25) | 11 (3) | 3 (2) | 8.07 (2.91-22.40) | <.001 | 13.33 (3.29-54.05) | <.001 |
| MSH2 | 2 (13) | 5 (2) | 3 (2) | 8.33 (1.75-39.67) | .008 | 6.25 (1.13-34.67) | .036 |
| MLH1 | 1 (6) | 1 (0.3) | 1 (0.7) | 20.81 (1.36-317.87) | .029 | 9.38 (0.62-142.82) | .107 |
| MSH6 | 1 (6) | 6 (2) | 0 | 3.47 (0.44-27.13) | .236 | – | – |
| PMS2 | 0 | 4 (1) | 0 | 2.18 (0.12-38.92) | .595 | – | – |
| Any HRD alterations | 8 (50) | 44 (13) | 29 (19) | 3.78 (2.16-6.64) | <.0001 | 2.59 (1.44-4.66) | .002 |
| BRCA1 | 1 (6) | 4 (1) | 1 (0.7) | 5.20 (0.62-43.92) | .130 | 9.38 (0.62-142.82) | .107 |
| BRCA2 | 4 (25) | 11 (3) | 19 (13) | 7.57 (2.71-21.17) | <.001 | 1.95 (0.76-5.02) | .168 |
| ATM | 3 (19) | 24 (7) | 7 (7.3) | 2.60 (0.87-7.74) | .086 | 4.02 (1.15-14.03) | .029 |
| PALB2 | 0 | 5 (2) | 0 | 1.79 (0.10-30.99) | .690 | – | – |
| CDK12 | 0 | 5 (2) | 7 (5) | 1.25 (0.07-21.70) | .878 | 0.592 (0.04-9.92) | .716 |
| Wnt-pathway | 6 (38) | 27 (8) | 19 (13) | 4.63 (2.23-9.58) | <.0001 | 2.96 (1.39-6.33) | .005 |
| CTNNB1 | 3 (19) | 9 (3) | 6 (4) | 6.94 (2.08-23.18) | .002 | 4.69 (1.29-16.97) | .019 |
| APC | 3 (19) | 18 (5) | 13 (9) | 3.47 (1.14-10.57) | .029 | 2.16 (0.69-6.80) | .186 |
| PI3K-mTOR pathway | 8 (50) | 103 (31) | 73 (49) | 1.62 (0.97-2.71) | .068 | 1.03 (0.61-1.72) | .918 |
| PTEN | 3 (19) | 58 (17) | 61 (41) | 1.08 (0.38-3.07) | .890 | 0.46 (0.16-1.30) | .144 |
| PIK3CA | 3 (19) | 16 (5) | 8 (5) | 3.90 (1.27-12.04) | .018 | 3.52 (1.04-11.94) | .044 |
| AKT1 | 2 (13) | 7 (2) | 2 (1) | 5.95 (1.34-26.37) | .019 | 9.38 (1.41-62.12) | .020 |
| TSC2 | 0 | 5 (2) | 6 (4) | 1.79 (0.10-31.00) | .690 | 0.68 (0.04-11.61) | .792 |
| Other ETS fusions |
3 (19) | 199 (60) | 84 (56) | 0.31 (0.11-0.87) | .027 | 0.33 (0.12-0.94) | .037 |
| TP53 | 2 (13) | 25 (8) | 80 (54) | 1.67 (0.43-6.42) | .459 | 0.23 (0.06-0.86) | .029 |
Note: P values and RR are in comparison to the lung-only patients. Mutational frequencies for comparator datasets were derived from either the primary publications or extracted from cBioPortal.16-19 P < .01 were considered of significance to account for multiple comparisons and are bolded for emphasis. Abbreviations: CI, confidence interval; HRD, homologous-recombination deficiency; mHSPC, metastatic hormone-sensitive prostate cancer; MMR, mismatch repair; RR, relative risks; SU2C-PCF, Stand Up To Cancer-Prostate Cancer Foundation; TCGA, The Cancer Genome Atlas.
TCGA data set is comprised of 333 men with localized prostate cancer.16
SU2C-PCF International Prostate Cancer Dream Team discovery set is comprised of 150 men with metastatic castration-resistant prostate cancer. Genomic landscape of this population has been previously published.17