HYENA detects oncogenes activated by distal enhancers in cancer.

IF 16.6 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Nucleic Acids Research Pub Date : 2024-09-09 DOI:10.1093/nar/gkae646

Anqi Yu, Ali E Yesilkanal, Ashish Thakur, Fan Wang, Yang Yang, William Phillips, Xiaoyang Wu, Alexander Muir, Xin He, Francois Spitz, Lixing Yang

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Abstract

Somatic structural variations (SVs) in cancer can shuffle DNA content in the genome, relocate regulatory elements, and alter genome organization. Enhancer hijacking occurs when SVs relocate distal enhancers to activate proto-oncogenes. However, most enhancer hijacking studies have only focused on protein-coding genes. Here, we develop a computational algorithm 'HYENA' to identify candidate oncogenes (both protein-coding and non-coding) activated by enhancer hijacking based on tumor whole-genome and transcriptome sequencing data. HYENA detects genes whose elevated expression is associated with somatic SVs by using a rank-based regression model. We systematically analyze 1146 tumors across 25 types of adult tumors and identify a total of 108 candidate oncogenes including many non-coding genes. A long non-coding RNA TOB1-AS1 is activated by various types of SVs in 10% of pancreatic cancers through altered 3-dimensional genome structure. We find that high expression of TOB1-AS1 can promote cell invasion and metastasis. Our study highlights the contribution of genetic alterations in non-coding regions to tumorigenesis and tumor progression.

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HYENA 检测癌症中由远端增强子激活的癌基因。

癌症中的体细胞结构变异（SVs）会改变基因组中的 DNA 含量，重新定位调控元件，并改变基因组的组织结构。当 SVs 迁移远端增强子以激活原癌基因时，就会发生增强子劫持。然而，大多数增强子劫持研究只关注蛋白编码基因。在这里，我们开发了一种名为 "HYENA "的计算算法，根据肿瘤全基因组和转录组测序数据来识别被增强子劫持激活的候选癌基因（包括蛋白编码基因和非编码基因）。HYENA 通过使用基于等级的回归模型来检测其表达升高与体细胞 SV 相关的基因。我们对 25 种成人肿瘤中的 1146 种肿瘤进行了系统分析，共鉴定出 108 个候选癌基因，其中包括许多非编码基因。在 10% 的胰腺癌中，长非编码 RNA TOB1-AS1 通过改变三维基因组结构被各种类型的 SV 激活。我们发现，TOB1-AS1的高表达可促进细胞侵袭和转移。我们的研究强调了非编码区的基因改变对肿瘤发生和发展的贡献。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nucleic Acids Research 生物-生化与分子生物学

CiteScore

27.10

自引率

4.70%

发文量

1057

审稿时长

2 months

期刊介绍： Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.