Profiling of 3D genome organization in nasopharyngeal cancer needle biopsy patient samples by a modified Hi-C approach

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...

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Main Authors: Animesh, Sambhavi, Choudhary, Ruchi, Wong, Bertrand Jern Han, Koh, Charlotte Tze Jia, Ng, Xin Yi, Tay, Joshua Kai Xun, Chong, Wan-Qin, Jian, Han, Chen, Leilei, Goh, Boon Cher, Fullwood, Melissa Jane
Other Authors: School of Biological Sciences
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Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/154181
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1541812023-02-28T17:11:11Z Profiling of 3D genome organization in nasopharyngeal cancer needle biopsy patient samples by a modified Hi-C approach Animesh, Sambhavi Choudhary, Ruchi Wong, Bertrand Jern Han Koh, Charlotte Tze Jia Ng, Xin Yi Tay, Joshua Kai Xun Chong, Wan-Qin Jian, Han Chen, Leilei Goh, Boon Cher Fullwood, Melissa Jane School of Biological Sciences National University of Singapore Science::Biological sciences Nasopharyngeal Cancer Chromatin Organization 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. Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Published version This research was supported by the National Research Foundation (NRF) Singapore through an NRF Fellowship awarded to MF (NRF-NRFF2012-054) and NTU start-up funds awarded to MF and by the RNA Biology Center at the Cancer Science Institute of Singapore, NUS, as part of funding under the Singapore Ministry of Education Academic Research Fund Tier 3 awarded to Daniel Tenen as lead PI with MF as coinvestigator (MOE2014-T3-1-006). This research was also supported by a National Research Foundation Competitive Research Programme grant awarded to Vinay Tergaonkar as lead PI and MF as co-PI (NRF-CRP17-2017-02), by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centres of Excellence initiative, and by the Ministry of Education Tier II grant awarded to MF (T2EP30120-0020). 2022-06-08T08:17:22Z 2022-06-08T08:17:22Z 2021 Journal Article Animesh, S., Choudhary, R., Wong, B. J. H., Koh, C. T. J., Ng, X. Y., Tay, J. K. X., Chong, W., Jian, H., Chen, L., Goh, B. C. & Fullwood, M. J. (2021). Profiling of 3D genome organization in nasopharyngeal cancer needle biopsy patient samples by a modified Hi-C approach. Frontiers in Genetics, 12, 673530-. https://dx.doi.org/10.3389/fgene.2021.673530 1664-8021 https://hdl.handle.net/10356/154181 10.3389/fgene.2021.673530 34539729 2-s2.0-85115167981 12 673530 en NRF-NRFF2012-054 MOE2014-T3-1-006 NRF-CRP17-2017-02 T2EP30120-0020 Frontiers in Genetics © 2021 Animesh, Choudhary, Wong, Koh, Ng, Tay, Chong, Jian, Chen, Goh and Fullwood. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Nasopharyngeal Cancer
Chromatin Organization
spellingShingle Science::Biological sciences
Nasopharyngeal Cancer
Chromatin Organization
Animesh, Sambhavi
Choudhary, Ruchi
Wong, Bertrand Jern Han
Koh, Charlotte Tze Jia
Ng, Xin Yi
Tay, Joshua Kai Xun
Chong, Wan-Qin
Jian, Han
Chen, Leilei
Goh, Boon Cher
Fullwood, Melissa Jane
Profiling of 3D genome organization in nasopharyngeal cancer needle biopsy patient samples by a modified Hi-C approach
description 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.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Animesh, Sambhavi
Choudhary, Ruchi
Wong, Bertrand Jern Han
Koh, Charlotte Tze Jia
Ng, Xin Yi
Tay, Joshua Kai Xun
Chong, Wan-Qin
Jian, Han
Chen, Leilei
Goh, Boon Cher
Fullwood, Melissa Jane
format Article
author Animesh, Sambhavi
Choudhary, Ruchi
Wong, Bertrand Jern Han
Koh, Charlotte Tze Jia
Ng, Xin Yi
Tay, Joshua Kai Xun
Chong, Wan-Qin
Jian, Han
Chen, Leilei
Goh, Boon Cher
Fullwood, Melissa Jane
author_sort Animesh, Sambhavi
title Profiling of 3D genome organization in nasopharyngeal cancer needle biopsy patient samples by a modified Hi-C approach
title_short Profiling of 3D genome organization in nasopharyngeal cancer needle biopsy patient samples by a modified Hi-C approach
title_full Profiling of 3D genome organization in nasopharyngeal cancer needle biopsy patient samples by a modified Hi-C approach
title_fullStr Profiling of 3D genome organization in nasopharyngeal cancer needle biopsy patient samples by a modified Hi-C approach
title_full_unstemmed Profiling of 3D genome organization in nasopharyngeal cancer needle biopsy patient samples by a modified Hi-C approach
title_sort profiling of 3d genome organization in nasopharyngeal cancer needle biopsy patient samples by a modified hi-c approach
publishDate 2022
url https://hdl.handle.net/10356/154181
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