《英文文献/摘要翻译》站在时间尽头2012

9、Mutational landscape of metastatic cancer

　　To gain insight into the overall genomic differences between primary and metastatic cancer, we compared the mutational burden in the Hartwig Medical Foundation (HMF) metastatic cohort with the Pancancer Analysis of Whole Genomes (PCAWG) dataset, which, to our knowledge, is the largest comparable whole-genome sequenced tumour cohort (n = 2,583) available so far, and which has 95% of biopsies taken from treatment-naive primary tumours.
　　为深入了解原发癌与转移癌的整个基因组差异，我们比较了哈特威格医学基金会（HMF）转移队列的突变负荷，与全基因组泛癌症分析（PCAWG）数据集，这是据我们所知，迄今为止最宏大的、具可比性的、可研究的全基因组测序肿瘤群（n = 2，583），其中95%活检取自初次治疗的原发性肿瘤。

　　In general, the SNV mutational load does not seem to be indicative for disease progression as it is not significantly different in this study compared with the PCAWG for most cancer types.
　　一般而言，单核苷酸变异的突变负荷似乎并不表示病情进展，因为在这项研究中，它与大多数癌症类型的全基因组泛癌症分析相比，并没有显著差异。

　　Prostate and breast cancer are clear exceptions with structurally higher mutational loads, which potentially reflects relevant tumour biology and is, for prostate cancer, consistent with other reports.
　　前列腺癌和乳腺癌是结构上突变负荷较高的明显例外，这可能反映了相关的肿瘤生物学内容。对于前列腺癌，结果与其他报告一致。

　　CNS tumours also have a higher mutational load that is explained by the different age distributions of the cohorts.
　　中枢神经系统肿瘤的突变负荷也较高，这可以用同队列不同的年龄分布来解释。

　　By contrast, the mutational loads of indels, MNVs and SVs are significantly higher across nearly all cancer types analysed.
　　相较而言，在几乎所有被分析到的癌症类型中，多核苷酸变异和结构变异的突变负荷都高得惊人。

　　This is most notable for prostate cancer, in which we observe a more than fourfold increased rate of MNVs, indels and SVs.
　　前列腺癌是最值得注意的，在其中我们观察到，多核苷酸变异、插入缺失和结构变异的增长率超过原来的四倍。

　　Although these observations may represent the advancement of disease and the higher rate of certain mutational processes in metastatic cancers, they are also partially due to differences in sequencing depth and bioinformatic analysis pipelines.
　　虽然这些观察结果可能代表了病情发展和转移癌某些突变过程的较高比例，但也有部分原因是测序深度和生物信息分析管道的差异。