Profiling of 3D Genome Organization in Nasopharyngeal Cancer Needle Biopsy Patient Samples by a Modified Hi-C Approach

通过改进的 Hi-C 方法对鼻咽癌针吸活检患者样本中的 3D 基因组组织进行分析

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作者:Sambhavi Animesh, Ruchi Choudhary, Bertrand Jern Han Wong, Charlotte Tze Jia Koh, Xin Yi Ng, Joshua Kai Xun Tay, Wan-Qin Chong, Han Jian, Leilei Chen, Boon Cher Goh, Melissa Jane Fullwood

Abstract

Nasopharyngeal cancer (NPC), a cancer derived from epithelial cells in the nasopharynx, is a cancer common in China, Southeast Asia, and Africa. The three-dimensional (3D) genome organization of nasopharyngeal cancer is poorly understood. A major challenge in understanding the 3D genome organization of cancer samples is the lack of a method for the characterization of chromatin interactions in solid cancer needle biopsy samples. Here, we developed Biop-C, a modified in situ Hi-C method using solid cancer needle biopsy samples. We applied Biop-C to characterize three nasopharyngeal cancer solid cancer needle biopsy patient samples. We identified topologically associated domains (TADs), chromatin interaction loops, and frequently interacting regions (FIREs) at key oncogenes in nasopharyngeal cancer from the Biop-C heatmaps. We observed that the genomic features are shared at some important oncogenes, but the patients also display extensive heterogeneity at certain genomic loci. On analyzing the super enhancer landscape in nasopharyngeal cancer cell lines, we found that the super enhancers are associated with FIREs and can be linked to distal genes via chromatin loops in NPC. Taken together, our results demonstrate the utility of our Biop-C method in investigating 3D genome organization in solid cancers.

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