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首页> 外文期刊>EBioMedicine >A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men
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A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men

机译：LSAMP的新型基因组改变与非裔美国男性的侵略性前列腺癌有关

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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.
机译：鉴于世界人口种族分布的变化，在全球范围内评估癌症基因组引起了极大的兴趣。由于他们的前列腺癌（CaP）发病率和死亡率异常高，我们将研究重点放在了非洲血统的男性上。我们提出了系统的全基因组分析，揭示了区分非裔美国人（AA）和高加索美国人（CA）CaP基因组的改变。我们发现以AAAMP男性的肿瘤中普遍存在的LSAMP基因座为中心，在染色体3q13.31上出现了反复缺失（累计分析435例患者：全基因组序列14例; FISH评估101例; SNP阵列320例）。值得注意的是，这种缺失的携带者经历了更快的疾病进展。相反，与来自CA的前列腺肿瘤相比，AA前列腺肿瘤中CaP中的PTEN和ERG共同驱动因子改变明显更低。而且，AA中染色体间重排的频率显着高于CA肿瘤。这些发现揭示了不同祖先群体中CaP的体细胞突变分布不同，这对精确医学策略具有影响。

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