Genomic abnormalities, including structural variation (SV), copy number variation (CNV), single-nucleotide polymorphism (SNP), homogenously staining regions (HSR) and extrachromosomal DNA (ecDNA), are strongly associated with cancer, rare diseases and infertility. A robust technology to simultaneously detect these genomic abnormalities is highly desired for clinical diagnosis and basic research. In this study, we developed a simple and cost-effective method - multiple genetic abnormality sequencing (MGA-Seq) - to simultaneously detect SNPs, CNVs, SVs, ecDNA and HSRs in a single tube. This method has been successfully applied in both cancer cell lines and clinical tumour samples and revealed that focal amplification in tumour tissue is substantially heterogeneous. Notably, we delineated the architecture of focal amplification and the ecDNA network by MGA-Seq, which facilitated the exploration of the regulation of gene expression in ecDNA. This method could be extensively applied for diagnosis and may greatly facilitate the investigation of the genomic mechanism for genetic diseases.

中文翻译：

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使用多重基因异常测序 (MGA-Seq) 可靠鉴定染色体外 DNA 和遗传变异

基因组异常，包括结构变异 (SV)、拷贝数变异 (CNV)、单核苷酸多态性 (SNP)、同源染色区域 (HSR) 和染色体外 DNA (ecDNA)，与癌症、罕见病和不育症密切相关。临床诊断和基础研究非常需要一种同时检测这些基因组异常的强大技术。在这项研究中，我们开发了一种简单且经济高效的方法 - 多重基因异常测序 (MGA-Seq) - 在单个试管中同时检测 SNP、CNV、SV、ecDNA 和 HSR。该方法已成功应用于癌细胞系和临床肿瘤样本，并揭示了肿瘤组织中的局灶性扩增基本上是异质的。尤其，我们通过 MGA-Seq 描绘了焦点扩增的结构和 ecDNA 网络，这有助于探索 ecDNA 中基因表达的调控。该方法可广泛应用于诊断，并可能极大地促进遗传病基因组机制的研究。