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Integrated epigenomic analysis identifies structural alterations associated with oncogenic gene expression in liposarcoma

ABSTRACT: Liposarcoma (LPS) is the most common soft-tissue sarcoma in adults. The two most frequent subtypes well differentiated (WD) and dedifferentiated (DD) LPS are often marked with the giant chromosome and the amplifications of chromosome 12q13-15. However, it remains unknown how this genomic aberrancy contributes to the dysregulation of the oncogenes. Here, we reported a comprehensive molecular characterization of both tumor and normal tissues from the same batch of LPS patients, including Hi-C, H3K27ac ChIP-seq, RNA-seq and WGS datasets. We identified a library of tumor-specific enhancers that may play a critical role in oncogenesis. We also demonstrated the enhancer co-amplification and hijacking events involved with proto-oncogenes such as MDM2, CDK4 and HMGA2, which have not been previously reported and as a novel mechanism to upregulate these genes. By combining Hi-C, optical mapping, Nanopore long reads and WGS data, we partially resolved complex structure variations (SVs) and reconstructed the local genome and the giant chromosome. We further validated the presence of multiple copies of MDM2 and CDK4 are located on the giant chromosome by fluorescent in situ hybridization (FISH). Consequently, this study provides a comprehensive resource for further research in LPS.

ORGANISM(S): Homo sapiens

PROVIDER: GSE201056 | GEO | 2023/03/03

REPOSITORIES: GEO

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