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首页> 外文期刊>Cancer research: The official organ of the American Association for Cancer Research, Inc >Mutational Landscape of Aggressive Prostate Tumors in African American Men
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Mutational Landscape of Aggressive Prostate Tumors in African American Men

机译:非洲裔美国人侵略性前列腺肿瘤的变异景观

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摘要

Prostate cancer is the most frequently diagnosed and second most fatal nonskin cancer among men in the United States. African American men are two times more likely to develop and die of prostate cancer compared with men of other ancestries. Previous whole genome or exome tumor-sequencing studies of prostate cancer have primarily focused on men of European ancestry. In this study, we sequenced and characterized somatic mutations in aggressive (Gleason >= 7, stage >= T2b) prostate tumors from 24 African American patients. We describe the locations and prevalence of small somatic mutations (up to 50 bases in length), copy number aberrations, and structural rearrangements in the tumor genomes compared with patient-matched normal genomes. We observed several mutation patterns consistent with previous studies, such as large copy number aberrations in chromosome 8 and complex rearrangement chains. However, TMPRSS2-ERG gene fusions and PTEN losses occurred in only 21% and 8% of the African American patients, respectively, far less common than in patients of European ancestry. We also identified mutations that appeared specific to or more common in African American patients, including a novel CDC27-OAT gene fusion occurring in 17% of patients. The genomic aberrations reported in this study warrant further investigation of their biologic significant role in the incidence and clinical outcomes of prostate cancer in African Americans.
机译:在美国男性中,前列腺癌是最常见的诊断方法,也是致命性第二高的非皮肤癌。与其他祖先的男性相比,非洲裔美国男性患前列腺癌和死亡的可能性高两倍。先前有关前列腺癌的全基因组或外显子组肿瘤测序研究主要集中于欧洲血统的男性。在这项研究中,我们对来自24位非裔美国人的侵袭性前列腺癌(Gleason> = 7,阶段> = T2b)的体细胞突变进行了测序和表征。我们描述了与患者匹配的正常基因组相比,小体细胞突变(长度最多50个碱基),拷贝数畸变和结构重排的位置和发生率。我们观察到了几种与先前研究一致的突变模式,例如8号染色体上的大拷贝数畸变和复杂的重排链。但是,TMPRSS2-ERG基因融合和PTEN丢失分别仅在21%和8%的非洲裔美国患者中发生,远不及欧洲血统的患者常见。我们还鉴定了在非裔美国人患者中似乎特异或更常见的突变,包括在17%的患者中发生的新型CDC27-OAT基因融合。这项研究中报道的基因组异常需要进一步研究其在非洲裔美国人中前列腺癌的发生率和临床结果中的生物学重要作用。

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