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线粒体突变促使前列腺癌入侵

作者:Jan Korbel, Thorsten Schlomm, Robert G. Bristow

众所周知,核基因突变能促进肿瘤的发生、侵袭和对治疗的反应。相反,在母系遗传的线粒体基因组中,突变的频率和作用,我们了解甚少。我们对384个限性前列腺癌患者的线粒体基因组进行测序,并确定了每个病人一个线粒体单核苷酸变异(mtsnv)的中位数。部分这些mtsnvs发生在复发性突变热点,并伴随侵袭性疾病。跟年纪大的相比,年轻的患者有较少的mtsnvs。我们展示了线粒体和核突变结构之间的紧密联系,在特定突变之间同时发生。例如,某些控制区mtsnvs同时发生,获得致癌基因MYC,而这些突变与患者生存率相关。这些数据表明前列腺癌中线粒体突变频繁,并提示前列腺癌中线粒体和线粒体突变结构之间的相互作用。

Panorama of mitochondrial mutations in prostate cancer. a The top panel displays the number of mtSNVs per patient sorted first by T-Category and then by the number of mtSNVs; histogram bars are colored by the average difference in the heteroplasmy fraction (∆HF) between tumor and normal samples, light-blue 20–40%, medium-blue 40–60%, dark-blue ≥60%. A heatmap showing the location of each mtSNV on the mitochondrial genome (middle), where the color of each dot represents ∆HF. The mitochondrial genome is represented on the left. The bottom panel shows the clinical covariates for all 384 patients: Age, Gleason Score, PSA, and T-Category. Bottom right: Associations between the covariates and number of mtSNVs. b Frequency and distribution of single-nucleotide variants (SNVs) within the mitochondrial genome. Mutation frequency normalized by dividing the number of mutations per locus of each patient by (length of the locus (kbp) × MCN). c Distribution of mtSNVs across the mitochondrial genome. mtSNVs were fairly evenly distributed across the genome (black bars) and recurrent mutation positions are indicated by the histogram

原文阅读

https://www.nature.com/articles/s41467-017-00377-y


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