Distinct genomic alterations in prostate cancers in Chinese and Western populations suggest alternative pathways of prostate carcinogenesis.
Distinct genomic alterations in prostate cancers in Chinese and Western populations suggest alternative pathways of prostate carcinogenesis.
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DOI：
10.1158/0008-5472.can-09-4074
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发表时间：
2010-07-01
期刊：
影响因子：
11.2
通讯作者：
Lu YJ
中科院分区：
文献类型：
--
作者：
Mao X;Yu Y;Boyd LK;Ren G;Lin D;Chaplin T;Kudahetti SC;Stankiewicz E;Xue L;Beltran L;Gupta M;Oliver RT;Lemoine NR;Berney DM;Young BD;Lu YJ
前列腺癌在西方男性中明显比亚洲男性更常见，但这种差异的基础仍不清楚。由于亚洲前列腺癌的基因组研究非常有限，我们使用全基因组的方法来揭示中国前列腺癌的基因组变化。我们发现在西方前列腺癌中常见的某些体细胞基因组改变的频率显著降低，包括涉及TMPRSS2：ERG融合基因的21q22.2-22.3缺失和导致PTEN失活的10q缺失。在选定的样本中，通过基于PCR的分子拷贝数计数证实了阵列结果。通过组织芯片样品的荧光原位杂交和免疫组织化学分析，进一步评估了这些基因组变化的不同频率。这些改变可能是导致临床发病率地区/种族差异的关键基因变化，可能是由西方男性接触的特定环境和/或遗传风险因素引起的。我们的发现表明，肿瘤在西方和中国人群中通过不同的致病机制发生。
Prostate cancer is significantly more common in Western men than Asian men, but the basis for this difference remains unknown. Since genomic studies of Asian prostate cancer are very limited, we used a genome-wide approach to reveal the genomic alterations in Chinese prostate cancers. We found a significant reduction in the frequency of certain somatic genomic changes that are commonly found in Western prostate cancers, including the 21q22.2-22.3 deletion, which involves the TMPRSS2:ERG fusion gene, and 10q deletion, which causes PTEN inactivation. Array results were confirmed by PCR-based molecular copy number counting in selected samples. The different frequency of these genomic changes was further evaluated by fluorescence in situ hybridization and immunohistochemistry analyses of tissue microarray samples. These alterations may be key genetic changes underlying the regional/ethnic difference in clinical incidence and may be induced by specific environmental and/or genetic risk factors that Western men are exposed to. Our findings suggest that tumors arise in Western and Chinese populations by alternative pathogenetic mechanisms.