Genetic Profiling of African American Patients With Prostatic Adenocarcinoma Metastatic to the Lymph Nodes: A Pilot Study.

IF 3.7 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Samuel Bidot, Jun Yin, Pengbo Zhou, Linsheng Zhang, Kristin K Deeb, Geoffrey Smith, Charles E Hill, Joanne Xiu, Mehmet A Bilen, Katherine B Case, Mazie Tinsley, Bradley Carthon, Lara R Harik
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Abstract

Context.—: 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.

Objective.—: To investigate the genomic alterations of prostatic adenocarcinoma metastatic to regional lymph nodes in African American patients, with an emphasis on SPOP mutation.

Design.—: 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.

Results.—: 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 significantly 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).

Conclusions.—: 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.

转移至淋巴结的非裔美国前列腺腺癌患者的基因图谱分析:一项试点研究。
背景前列腺腺癌的基因图谱数据主要来自白人患者。在非裔美国人中,前列腺腺癌的预后较差,因此可能存在不同的基因改变:研究非裔美国人转移至区域淋巴结的前列腺腺癌的基因组改变,重点是 SPOP 突变:我们回顾性研究了接受根治性前列腺切除术和淋巴结清扫术治疗的pN1前列腺腺癌非裔美国人患者。进行了全面的分子谱分析,并计算了雄激素受体信号转导评分:结果:共纳入 19 例患者。最常见的基因改变是 SPOP 突变(17 例中有 5 例;29.4% [95% CI:10.3-56.0])。虽然大多数基因改变都与雄激素受体信号转导评分较高有关,但突变 SPOP 只与中位数和四分位数间距 (IQR) 较低的雄激素受体信号转导评分有关(0.788 [IQR 0.765-0.791] 对 0.835 [IQR 0.828-0.842], P = .003)。在突变体 SPOP 中,SPOP 抑制剂 G3BP1 和 SPOP 底物的 mRNA 表达显示 AR 的表达显著下降(33.40 [IQR 28.45-36.30] 对 59.53 [IQR 53.10-72.83],P = .01)、TRIM24(3.95 [IQR 3.28-5.03] 对 9.80 [IQR 7.39-11.70] ,P = .008)和 NCOA3(15.19 [IQR 10.59-15.93] 对 21.88 [IQR 18.41-28.33] ,P = .046):非裔美国人转移性前列腺腺癌患者可能有更高的突变SPOP发生率(30%),而在SPOP底物表达较低的非选择人群中,突变SPOP发生率仅为10%。在我们的研究中,在SPOP突变的患者中,突变与SPOP底物表达和雄激素受体信号转导的降低有关,这使人们担心雄激素剥夺疗法在这部分患者中的疗效不理想。
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来源期刊
CiteScore
9.20
自引率
2.20%
发文量
369
审稿时长
3-8 weeks
期刊介绍: Welcome to the website of the Archives of Pathology & Laboratory Medicine (APLM). This monthly, peer-reviewed journal of the College of American Pathologists offers global reach and highest measured readership among pathology journals. Published since 1926, ARCHIVES was voted in 2009 the only pathology journal among the top 100 most influential journals of the past 100 years by the BioMedical and Life Sciences Division of the Special Libraries Association. Online access to the full-text and PDF files of APLM articles is free.
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