Spectrum of mitochondrial genomic variation and associated clinical presentation of prostate cancer in South African men.
Spectrum of mitochondrial genomic variation and associated clinical presentation of prostate cancer in South African men.
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DOI：
10.1002/pros.23126
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Hayes VM
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文献类型：
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作者：
McCrow JP;Petersen DC;Louw M;Chan EK;Harmeyer K;Vecchiarelli S;Lyons RJ;Bornman MS;Hayes VM
非洲裔美国男性的前列腺癌发病率和死亡率显著增加，但在撒哈拉以南非洲人口中进行的研究有限。由于线粒体控制能量代谢和细胞凋亡，我们推测线粒体基因组中的体细胞突变是侵袭性前列腺癌发生的候选驱动因素。我们使用了87名南非男性(77名非洲血统)的匹配血液和前列腺组织样本来对完整的线粒体基因组进行深度测序。临床表现倾向于侵袭性疾病(格里森评分7，%)，并与非前列腺癌患者相比，无论是否伴有良性前列腺增生。我们鉴定了144个体细胞线粒体DNA单核苷酸变异(SNV)，其中80个是在39名表现为侵袭性疾病的男性中观察到的。体细胞mtDNA SNV的数目和频率均与病理分期有关。除了使迄今发现的体细胞前列腺癌相关线粒体基因组突变总数翻一番外，我们还将突变负载与非洲血统男性的侵袭性前列腺癌状态联系起来。前列腺癌76：349-358,2016。©2015作者。《前列腺癌》由威利期刊出版公司出版。
Prostate cancer incidence and mortality rates are significantly increased in African–American men, but limited studies have been performed within Sub–Saharan African populations. As mitochondria control energy metabolism and apoptosis we speculate that somatic mutations within mitochondrial genomes are candidate drivers of aggressive prostate carcinogenesis. We used matched blood and prostate tissue samples from 87 South African men (77 with African ancestry) to perform deep sequencing of complete mitochondrial genomes. Clinical presentation was biased toward aggressive disease (Gleason score >7, 64%), and compared with men without prostate cancer either with or without benign prostatic hyperplasia. We identified 144 somatic mtDNA single nucleotide variants (SNVs), of which 80 were observed in 39 men presenting with aggressive disease. Both the number and frequency of somatic mtDNA SNVs were associated with higher pathological stage. Besides doubling the total number of somatic PCa‐associated mitochondrial genome mutations identified to date, we associate mutational load with aggressive prostate cancer status in men of African ancestry. Prostate 76:349–358, 2016. © 2015 The Authors. The Prostate published by Wiley Periodicals, Inc.