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Weerachai Jaratlerdsiri^1,2, Jue Jiang^1,2, Tingting Gong^1,2,3

¹Ancestry and Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, Australia.

|August 31, 2022

概括

前列腺癌显示出显著的地理种族差异,特别是在非洲人口中. 这项研究确定了祖先特定的基因组变化和突变过程,揭示了影响临床结果的全球突变亚型,并突出了基因与环境的相互作用.

科学领域:

基因组学
癌症研究
人口遗传学

背景情况:

前列腺癌在非洲撒哈拉以南地区的死亡率较高,
导致这些差异的遗传和非遗传因素以及相关的突变过程在很大程度上是未知的.
非洲血统是前列腺癌的风险因素之一.

研究的目的:

为撒哈拉以南非洲地区提供全面的癌症基因组资源.
在前列腺癌中识别祖先特异性的遗传变异和突变特征.
建立基于祖先和突变过程的前列腺癌分子分类学.

主要方法:

从非洲和欧洲血统的患者获得183个未经治疗的前列腺癌样本的全基因组测序.
识别和分析大约200万个体质变异.
包括中国亚洲数据来定义和验证全球突变亚型 (GMS).

主要成果:

发现了重要的非洲祖先特异性发现,包括瘤突变负担增加,基因组变异增加以及特定的驱动基因 (NCOA2,STK19,DDX11L1,PCAT1,SETBP1).
由祖先区分的全球突变亚型 (GMS) 定义的前列腺癌分子分类学的发展.
确定GMS-B和GMS-D为非洲人群特有的,GMS-A为普遍的,GMS-C (副本数量损失) 作为非洲-欧洲受限的和预测不良结果的.

结论:

全球突变亚型揭示了前列腺癌的不同进化轨迹和突变过程.
共同的遗传和环境因素都可能导致前列腺癌的种族差异.
这些发现强调了在癌症基因组学研究中包括多样化的祖先的重要性,并表明GMS亚型可以作为内在和外在突变过程的代理.

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