Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and Walter Reed National Military Medical Center, Bethesda, MD 20814, USA.
Genomatix Software GmbH, MünchenE D-80335, Germany.
EBioMedicine. 2015 Oct 31;2(12):1957-64. doi: 10.1016/j.ebiom.2015.10.028. eCollection 2015 Dec.
Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP) incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA) and Caucasian American (CA) CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients). Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somatic mutations in CaP across ancestral groups, which have implications for precision medicine strategies.
鉴于世界人口的种族分布正在发生变化，从全球角度评估癌症基因组具有重要意义。我们专注于研究非洲裔男性，因为他们的前列腺癌（CaP）发病率和死亡率不成比例地更高。我们进行了系统的全基因组分析，揭示了区分非裔美国男性（AA）和白种裔美国男性（CA）CaP 基因组的改变。我们发现了染色体 3q13.31 上的一个反复缺失，该缺失以 LSAMP 基因座为中心，在 AA 男性的肿瘤中很常见（对 435 名患者的全基因组序列、14 名患者的 FISH 评估和 320 名患者的 SNP 芯片进行了累积分析）。值得注意的是，携带这种缺失的患者疾病进展更快。相比之下，AA 前列腺肿瘤中 PTEN 和 ERG 常见驱动改变明显低于 CA 前列腺肿瘤。此外，AA 肿瘤中染色体间重排的频率明显高于 CA 肿瘤。这些发现揭示了不同祖裔群体中 CaP 中分布不均的体细胞突变，这对精准医疗策略具有重要意义。
