Synergistic alterations in the multilevel chromatin structure anchor dysregulated genes in small cell lung cancer

Small cell lung cancer (SCLC) is an aggressive form of lung cancer that uniquely changes the chromosomal structure, although the basis of aberrant gene expression in SCLC remains largely unclear. Topologically associated domains (TADs) are structural and functional units of the human genome. Genetic...

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Autores principales:	Dan Guo, Qiu Xie, Shuai Jiang, Ting Xie, Yaru Li, Xin Huang, Fangyuan Li, Tingting Wang, Jian Sun, Anqi Wang, Zixin Zhang, Hao Li, Xiaochen Bo, Hebing Chen, Zhiyong Liang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	SCLC TARGET Hi-C TAD NanoString Tumorigenesis Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/70dd559a86354770ae7cc3d1fa802cad
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spelling	oai:doaj.org-article:70dd559a86354770ae7cc3d1fa802cad2021-11-14T04:31:42ZSynergistic alterations in the multilevel chromatin structure anchor dysregulated genes in small cell lung cancer2001-037010.1016/j.csbj.2021.11.003https://doaj.org/article/70dd559a86354770ae7cc3d1fa802cad2021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2001037021004682https://doaj.org/toc/2001-0370Small cell lung cancer (SCLC) is an aggressive form of lung cancer that uniquely changes the chromosomal structure, although the basis of aberrant gene expression in SCLC remains largely unclear. Topologically associated domains (TADs) are structural and functional units of the human genome. Genetic and epigenetic alterations in the cancer genome can lead to the disruption of TAD boundaries and may cause gene dysregulation. To understand the potential regulatory role of this process in SCLC, we developed the TAD boundary alteration–related gene identification in tumors (TARGET) computational framework, which enables the systematic identification of candidate dysregulated genes associated with altered TAD boundaries. Using TARGET to compare gene expression profiles between SCLC and normal human lung fibroblast cell lines, we identified >100 genes in this category, of which 24 were further verified in samples from patients with SCLC using NanoString. The analysis revealed synergistic chromatin structure alteration at the A/B compartment and TAD boundary levels that underlies aberrant gene expression in SCLC. TARGET is a novel and powerful tool that can be used to explore the relationship of chromatin structure alteration to gene dysregulation related to SCLC tumorigenesis, progression, and prognosis.Dan GuoQiu XieShuai JiangTing XieYaru LiXin HuangFangyuan LiTingting WangJian SunAnqi WangZixin ZhangHao LiXiaochen BoHebing ChenZhiyong LiangElsevierarticleSCLCTARGETHi-CTADNanoStringTumorigenesisBiotechnologyTP248.13-248.65ENComputational and Structural Biotechnology Journal, Vol 19, Iss , Pp 5946-5959 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SCLC TARGET Hi-C TAD NanoString Tumorigenesis Biotechnology TP248.13-248.65
spellingShingle	SCLC TARGET Hi-C TAD NanoString Tumorigenesis Biotechnology TP248.13-248.65 Dan Guo Qiu Xie Shuai Jiang Ting Xie Yaru Li Xin Huang Fangyuan Li Tingting Wang Jian Sun Anqi Wang Zixin Zhang Hao Li Xiaochen Bo Hebing Chen Zhiyong Liang Synergistic alterations in the multilevel chromatin structure anchor dysregulated genes in small cell lung cancer
description	Small cell lung cancer (SCLC) is an aggressive form of lung cancer that uniquely changes the chromosomal structure, although the basis of aberrant gene expression in SCLC remains largely unclear. Topologically associated domains (TADs) are structural and functional units of the human genome. Genetic and epigenetic alterations in the cancer genome can lead to the disruption of TAD boundaries and may cause gene dysregulation. To understand the potential regulatory role of this process in SCLC, we developed the TAD boundary alteration–related gene identification in tumors (TARGET) computational framework, which enables the systematic identification of candidate dysregulated genes associated with altered TAD boundaries. Using TARGET to compare gene expression profiles between SCLC and normal human lung fibroblast cell lines, we identified >100 genes in this category, of which 24 were further verified in samples from patients with SCLC using NanoString. The analysis revealed synergistic chromatin structure alteration at the A/B compartment and TAD boundary levels that underlies aberrant gene expression in SCLC. TARGET is a novel and powerful tool that can be used to explore the relationship of chromatin structure alteration to gene dysregulation related to SCLC tumorigenesis, progression, and prognosis.
format	article
author	Dan Guo Qiu Xie Shuai Jiang Ting Xie Yaru Li Xin Huang Fangyuan Li Tingting Wang Jian Sun Anqi Wang Zixin Zhang Hao Li Xiaochen Bo Hebing Chen Zhiyong Liang
author_facet	Dan Guo Qiu Xie Shuai Jiang Ting Xie Yaru Li Xin Huang Fangyuan Li Tingting Wang Jian Sun Anqi Wang Zixin Zhang Hao Li Xiaochen Bo Hebing Chen Zhiyong Liang
author_sort	Dan Guo
title	Synergistic alterations in the multilevel chromatin structure anchor dysregulated genes in small cell lung cancer
title_short	Synergistic alterations in the multilevel chromatin structure anchor dysregulated genes in small cell lung cancer
title_full	Synergistic alterations in the multilevel chromatin structure anchor dysregulated genes in small cell lung cancer
title_fullStr	Synergistic alterations in the multilevel chromatin structure anchor dysregulated genes in small cell lung cancer
title_full_unstemmed	Synergistic alterations in the multilevel chromatin structure anchor dysregulated genes in small cell lung cancer
title_sort	synergistic alterations in the multilevel chromatin structure anchor dysregulated genes in small cell lung cancer
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/70dd559a86354770ae7cc3d1fa802cad
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Synergistic alterations in the multilevel chromatin structure anchor dysregulated genes in small cell lung cancer

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