Yang Manqiu, Zhang Shufan, Jiang Rong, Chen Shaomu, Huang Moli
School of Biology and Basic Medical Sciences, Soochow University, 215123, Suzhou, China.
Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, 215006, Suzhou, China.
Oncogenesis. 2023 May 22;12(1):28. doi: 10.1038/s41389-023-00476-0.
In cancer, extrachromosomal circular DNA (ecDNA), or megabase-pair amplified circular DNA, plays an essential role in intercellular heterogeneity and tumor cell revolution because of its non-Mendelian inheritance. We developed circlehunter ( https://github.com/suda-huanglab/circlehunter ), a tool for identifying ecDNA from ATAC-Seq data using the enhanced chromatin accessibility of ecDNA. Using simulated data, we showed that circlehunter has an F1 score of 0.93 at 30× local depth and read lengths as short as 35 bp. Based on 1312 ecDNAs predicted from 94 publicly available datasets of ATAC-Seq assays, we found 37 oncogenes contained in these ecDNAs with amplification characteristics. In small cell lung cancer cell lines, ecDNA containing MYC leads to amplification of MYC and cis-regulates the expression of NEUROD1, resulting in an expression pattern consistent with the NEUROD1 high expression subtype and sensitive to Aurora kinase inhibitors. This showcases that circlehunter could serve as a valuable pipeline for the investigation of tumorigenesis.
在癌症中，染色体外环状DNA（ecDNA），即兆碱基对扩增环状DNA，因其非孟德尔遗传特性，在细胞间异质性和肿瘤细胞演变中发挥着重要作用。我们开发了circlehunter（https://github.com/suda-huanglab/circlehunter），这是一种利用ecDNA增强的染色质可及性从ATAC-Seq数据中识别ecDNA的工具。通过模拟数据，我们表明circlehunter在30倍局部深度和短至35 bp的读长情况下，F1分数为0.93。基于从94个公开可用的ATAC-Seq检测数据集预测的1312个ecDNA，我们发现这些ecDNA中包含37个具有扩增特征的癌基因。在小细胞肺癌细胞系中，含有MYC的ecDNA导致MYC扩增并顺式调节NEUROD1的表达，从而产生与NEUROD1高表达亚型一致的表达模式，并且对极光激酶抑制剂敏感。这表明circlehunter可作为研究肿瘤发生的有价值工具。
