CDKN1B Deletions are Associated with Metastasis in African American Men with Clinically Localized, Surgically Treated Prostate Cancer

Abstract

Purpose: The potential biological determinants of aggressive prostate cancer (PCa) in African American (AA) men are unknown. Here we characterize PCa genomic alterations in the largest cohort to date of AA men with clinical follow-up for metastasis, with the aim to elucidate the key molecular drivers associated with poor prognosis in this population. Experimental Design: Targeted sequencing was retrospectively performed on 205 prostate tumors from AA men treated with radical prostatectomy (RP) to examine somatic genomic alterations and percent genome alteration (PGA). Cox proportional hazards analyses assessed the association of genomic alterations with risk of metastasis. Results: At RP, 71% (145/205) of patients had grade group ³3 disease, and 49% (99/202) were non-organ-confined. The median PGA was 3.7% (IQR 0.9-9.4%) and differed by pathologic grade (pSPOP (11.2%), FOXA1 (8.3%), and TP53 (3.9%). The most common loci altered at the copy number level were CDKN1B (6.3%), CHD1 (4.4%), and PTEN (3.4%). TP53 mutations and deep deletions in CDKN1B were associated with increased risks of metastasis on multivariable analyses (TP53: HR 9.5, 95% CI 2.2-40.6, p=0.002; CDKN1B: HR 6.7, 95% CI 1.3-35.2, p=0.026). Conclusions: Overall, PGA, somatic TP53 mutations, and a novel finding of deep deletions in CDKN1B were associated with poor prognosis in AA men. These findings require confirmation in additional AA cohorts.