CDKN1B Deletions are Associated with Metastasis in African American Men with Clinically Localized, Surgically Treated Prostate Cancer.
Clin Cancer Res
; 26(11): 2595-2602, 2020 06 01.
Article
en En
| MEDLINE
| ID: mdl-31969336
ABSTRACT
PURPOSE:
The potential biological determinants of aggressive prostate cancer in African American (AA) men are unknown. Here we characterize prostate cancer 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. EXPERIMENTALDESIGN:
Targeted sequencing was retrospectively performed on 205 prostate tumors from AA men treated with radical prostatectomy (RP) to examine somatic genomic alterations and percent of the genome with copy-number alterations (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 ≥3 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 (P < 0.001) and stage (P = 0.02). Median follow-up was 5 years. AA men with the highest quartile of PGA had increased risks of metastasis (multivariable HR = 13.45; 95% CI, 2.55-70.86; P = 0.002). The most common somatic mutations were SPOP (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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Prostatectomía
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Neoplasias de la Próstata
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Negro o Afroamericano
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Biomarcadores de Tumor
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Eliminación de Gen
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Inhibidor p27 de las Quinasas Dependientes de la Ciclina
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Recurrencia Local de Neoplasia
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2020
Tipo del documento:
Article