【黄子按曰】：最新一期的自然杂志上有一篇关于肿瘤与环状的染色体外DNA（ecDNA）的文章，对于基础探索与转化研究具有重要启示。由于几乎一半的人类肿瘤存在ecDNA，其频度虽然因肿瘤类型而异，但在正常细胞中却是几乎找不到的（这里，我觉得可能的例外是发育中的T细胞和B细胞VDJ重排时？），因此ecDNA本身应该算是一个非常特异的肿瘤标志物了，虽然敏感性因肿瘤类型而异。整个液体活检同行大概都在想：看看癌症样本肿瘤细胞内的ecDNA能否有办法从血液中检测出来？这里抛砖引玉，先将该论文的题目与文摘翻译如下。

染色体外原癌基因扩增驱动肿瘤进化与遗传异质性

人类细胞有23对染色体。但是，在肿瘤中，基因可能在染色体上或环状的染色体外DNA（circular extrachromosomal DNA，ecDNA）上扩增，尽管ecDNA出现的频率与功能上的重要性尚未可知。我们对17种不同肿瘤进行了全基因组测序，结构建模和细胞遗传分析，包括对2572个分裂中期细胞染色体结构与功能的分析，开发了名为ECdetect的软件包用于无偏倚的整合ecDNA检测与分析。这里，我们的结果显示，几乎一半的人类肿瘤存在ecDNA；其频度因肿瘤类型而异，但在正常细胞中是几乎找不到的。驱动型原癌基因的扩增在ecDNA中最为常见，从而增加了其转录本水平。数学建模预测，ecDNA扩增比染色体扩增能更为有效地增加原癌基因拷贝数和肿瘤内异质性。我们通过定量分析癌症样本证实了这些预测。这些结果提示，ecDNA有助于癌症的加速进化。

Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity

Human cells have twenty-three pairs of chromosomes. In cancer, however, genes can be amplified in chromosomes or in circular extrachromosomal DNA (ecDNA), although the frequency and functional importance of ecDNA are not understood. We performed whole-genome sequencing, structural modelling and cytogenetic analyses of 17 different cancer types, including analysis of the structure and function of chromosomes during metaphase of 2,572 dividing cells, and developed a software package called ECdetect to conduct unbiased, integrated ecDNA detection and analysis. Here we show that ecDNA was found in nearly half of human cancers; its frequency varied by tumour type, but it was almost never found in normal cells. Driver oncogenes were amplified most commonly in ecDNA, thereby increasing transcript level. Mathematical modelling predicted that ecDNA amplification would increase oncogene copy number and intratumoural heterogeneity more effectively than chromosomal amplification. We validated these predictions by quantitative analyses of cancer samples. The results presented here suggest that ecDNA contributes to accelerated evolution in cancer.