Genetic profiling data of prostatic adenocarcinoma are derived from predominantly White patients. In African Americans, prostatic adenocarcinoma has a poorer prognosis, raising the possibility of distinct genetic alterations.
To investigate the genomic alterations of prostatic adenocarcinoma metastatic to regional lymph nodes in African American patients, with an emphasis on SPOP mutation.
We retrospectively reviewed African American patients with pN1 prostatic adenocarcinoma managed with radical prostatectomy and lymph node dissection. Comprehensive molecular profiling was performed, and androgen receptor signaling scores were calculated.
Nineteen patients were included. The most frequent genetic alteration was SPOP mutations (5 of 17; 29.4% [95% CI: 10.3–56.0]). While most alterations were associated with a high androgen receptor signaling score, mutant SPOP was exclusively associated with a low median and interquartile range (IQR) androgen receptor signaling score (0.788 [IQR 0.765–0.791] versus 0.835 [IQR 0.828–0.842], P = .003). In mutant SPOP, mRNA expression of SPOP inhibitor G3BP1 and SPOP substrates showed a significant decreased expression of AR (33.40 [IQR 28.45–36.30] versus 59.53 [IQR 53.10–72.83], P = .01), TRIM24 (3.95 [IQR 3.28–5.03] versus 9.80 [IQR 7.39–11.70], P = .008), and NCOA3 (15.19 [IQR 10.59–15.93] versus 21.88 [IQR 18.41–28.33], P = .046).
African American patients with metastatic prostate adenocarcinoma might have a higher prevalence of mutant SPOP (30%), compared to ∼10% in unselected cohorts with lower expressions of SPOP substrates. In our study, in patients with mutant SPOP, the mutation was associated with decreased SPOP substrate expression and androgen receptor signaling, raising concern for suboptimal efficacy of androgen deprivation therapy in this subset of patients.
This research was supported in part by the Dunwoody Golf Club Prostate Cancer Research Award, a philanthropic award provided by the Winship Cancer Institute of Emory University.
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Yin and Xiu are employees of Caris Life Sciences. The other authors have no relevant financial interest in the products or companies described in this article.
The contents of the manuscript are original research that has been presented as a poster at the United States and Canadian Academy of Pathologist meeting; March 22, 2022; Los Angeles, California.