Mutational Landscape of Aggressive Prostate Tumors in African American Men.
Mutational Landscape of Aggressive Prostate Tumors in African American Men.
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DOI：
10.1158/0008-5472.can-15-1787
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发表时间：
2016-04-01
期刊：
影响因子：
11.2
通讯作者：
Witte JS
中科院分区：
文献类型：
--
作者：
Lindquist KJ;Paris PL;Hoffmann TJ;Cardin NJ;Kazma R;Mefford JA;Simko JP;Ngo V;Chen Y;Levin AM;Chitale D;Helfand BT;Catalona WJ;Rybicki BA;Witte JS
前列腺癌是美国男性中最常见的诊断和第二大致命的非皮肤癌。非裔美国人患前列腺癌和死于前列腺癌的可能性是其他血统的男性的两倍。以前的前列腺癌全基因组或外显子组肿瘤测序研究主要集中在欧洲血统的男性身上。在这项研究中，我们对来自24名非洲裔美国人患者的侵袭性（Gleason ≥7，≥ T2 b期）前列腺肿瘤的体细胞突变进行了测序和表征。我们描述的位置和患病率的小体细胞突变（长达50个碱基），拷贝数畸变，和结构重排的肿瘤基因组与患者匹配的正常基因组相比。我们观察到几个突变模式与以前的研究一致，如8号染色体的大拷贝数畸变和复杂的重排链。然而，TMPRSS 2-ERG基因融合和PTEN丢失分别仅发生在21%和8%的非裔美国人患者中，远低于欧洲血统的患者。我们还发现了在非裔美国人患者中出现的特异性或更常见的突变，包括17%的患者中发生的新型CDC 27-OAT基因融合。本研究中报告的基因组畸变需要进一步研究其在非裔美国人前列腺癌发病率和临床结局中的生物学意义。
Prostate cancer is the most frequently diagnosed and second most fatal non-skin 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 biological significance in the incidence and clinical outcomes of prostate cancer in African Americans.