脂肪肉瘤（LPS）是成人软组织肉瘤中最常见的一种类型，有两个主要亚型，即分化良好型和去分化型。这两个亚型都以携带高拷贝数已知癌基因的病理性巨大环或标记染色体为特征。在这里，我们报告了来自相同LPS患者的肿瘤和正常组织的全面分子特征，包括全基因组测序（WGS）、转录组、增强子图谱和基因组范围的Hi-C 3D基因组结构。鉴定了肿瘤特异性转录本和调控元素，并发现了增强子共同扩增和劫持事件，这些是调控癌基因如MDM2、CDK4和HMGA2的新机制。结合Hi-C、光学图谱、纳米孔长读取和WGS数据，部分解析了复杂的结构变异，并重建了局部基因组和巨大染色体。总体而言，这项研究为LPS研究提供了全面的资源，并深入了解了改变的增强子和3D基因组如何在癌症基因调控中发挥作用。

Liposarcoma (LPS) is the most common soft-tissue sarcoma in adults with two major subtypes, well differentiated and dedifferentiated. Both subtypes are characterized with the pathognomonic giant ring or marker chromosomes that harbor high copy-numbers of known oncogenes. Here, we reported a comprehensive molecular characterization of both tumor and normal tissues from the same LPS patients, including whole genome sequencing (WGS), transcriptome, enhancer landscape, and genome-wide 3D genome structure by Hi-C. Tumor-specific transcripts and regulatory elements were identified, and enhancer co-amplification and hijacking events were discovered as novel mechanisms upregulating oncogenes such as MDM2, CDK4 and HMGA2. Combining Hi-C, optical mapping, nanopore long reads and WGS data partially resolved complex structural variations and reconstructed the local genome and the giant chromosome. Overall, this study provides a comprehensive resource for LPS research and offers insights into how altered enhancers and the 3D genome contribute to gene dysregulation in cancer.