HYENA detects oncogenes activated by distal enhancers in cancer.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
    • Publication Information:
      Publication: 1992- : Oxford : Oxford University Press
      Original Publication: London, Information Retrieval ltd.
    • Subject Terms:
      Enhancer Elements, Genetic* ; Oncogenes* ; Neoplasms*/genetics ; Neoplasms*/pathology ; Gene Expression Regulation, Neoplastic*; Humans ; Algorithms ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism
    • 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.
      (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
    • Comments:
      Update of: bioRxiv. 2024 Apr 12:2023.01.09.523321. doi: 10.1101/2023.01.09.523321. (PMID: 38076958)
    • References:
      Cell. 2015 Dec 17;163(7):1641-54. (PMID: 26687355)
      Sci Adv. 2020 Jul 24;6(30):eaba3064. (PMID: 32832663)
      Nat Genet. 2018 Oct;50(10):1388-1398. (PMID: 30202056)
      Am J Cancer Res. 2018 Aug 01;8(8):1483-1498. (PMID: 30210918)
      Cell. 2015 May 21;161(5):1012-1025. (PMID: 25959774)
      Science. 2016 Mar 25;351(6280):1454-1458. (PMID: 26940867)
      Nat Genet. 2016 Feb;48(2):176-82. (PMID: 26656844)
      Science. 2017 Aug 18;357(6352):. (PMID: 28818916)
      Nature. 2017 Mar 2;543(7643):122-125. (PMID: 28178237)
      Am J Hum Genet. 2020 Nov 5;107(5):802-814. (PMID: 33022222)
      Nature. 2012 Apr 11;485(7398):376-80. (PMID: 22495300)
      Nat Genet. 2020 Aug;52(8):811-818. (PMID: 32632335)
      Mol Cell. 2020 May 7;78(3):554-565.e7. (PMID: 32213324)
      Nat Genet. 2018 Apr;50(4):613-620. (PMID: 29610481)
      Nat Genet. 2012 Dec;44(12):1316-20. (PMID: 23143595)
      Virchows Arch B Cell Pathol Incl Mol Pathol. 1992;61(5):295-306. (PMID: 1348891)
      Nat Genet. 2020 Mar;52(3):320-330. (PMID: 32025001)
      Nat Rev Cancer. 2018 Nov;18(11):696-705. (PMID: 30293088)
      Cell. 2014 Dec 18;159(7):1665-80. (PMID: 25497547)
      Nature. 2014 Apr 3;508(7494):98-102. (PMID: 24670643)
      Nat Rev Mol Cell Biol. 2016 Dec;17(12):771-782. (PMID: 27826147)
      Nature. 2016 Oct 13;538(7624):265-269. (PMID: 27706140)
      Cell Rep. 2016 May 31;15(9):2038-49. (PMID: 27210764)
      Nat Genet. 2017 Jan;49(1):65-74. (PMID: 27869826)
      Genome Biol. 2020 Jul 6;21(1):166. (PMID: 32631391)
      Nat Methods. 2020 Nov;17(11):1111-1117. (PMID: 33046897)
      Genome Res. 2014 Mar;24(3):390-400. (PMID: 24398455)
      Nat Rev Cancer. 2021 Jul;21(7):446-460. (PMID: 33953369)
      Cancer Cell. 2014 Sep 8;26(3):319-330. (PMID: 25155756)
      Nat Methods. 2021 Jun;18(6):661-668. (PMID: 34092790)
      Nature. 2020 Feb;578(7793):82-93. (PMID: 32025007)
      Nature. 2017 Jul 19;547(7663):311-317. (PMID: 28726821)
      Exp Ther Med. 2019 Dec;18(6):4249-4258. (PMID: 31772627)
      Nature. 2017 Oct 11;550(7675):204-213. (PMID: 29022597)
      Cell. 2019 Nov 27;179(6):1330-1341.e13. (PMID: 31761532)
      Nat Protoc. 2022 Jun;17(6):1518-1552. (PMID: 35478247)
      Nat Genet. 2022 May;54(5):725-734. (PMID: 35551308)
      Nature. 2010 Feb 18;463(7283):899-905. (PMID: 20164920)
      Cell. 2014 Apr 10;157(2):369-381. (PMID: 24703711)
      Hum Genet. 2021 Oct;140(10):1459-1469. (PMID: 34436670)
      Cell. 2018 Jan 25;172(3):393-407. (PMID: 29373828)
      Sci Adv. 2022 Jun 17;8(24):eabn9215. (PMID: 35704579)
      Nucleic Acids Res. 2021 Jan 8;49(D1):D1289-D1301. (PMID: 33179738)
      Nature. 2014 Jul 24;511(7510):428-34. (PMID: 25043047)
      Nature. 2019 Nov;575(7784):699-703. (PMID: 31748743)
      Cell. 2018 Jul 12;174(2):422-432.e13. (PMID: 29909987)
      Nature. 2009 Dec 10;462(7274):803-7. (PMID: 20010689)
      Gene. 2003 Mar 13;306:37-44. (PMID: 12657465)
      Gut. 2020 Jun;69(6):1039-1052. (PMID: 31542774)
      J Hepatol. 2010 Apr;52(4):594-604. (PMID: 20185200)
      Nat Rev Genet. 2013 Feb;14(2):125-38. (PMID: 23329113)
      Genome Biol. 2022 Mar 15;23(1):79. (PMID: 35292087)
      Cell. 1985 Jul;41(3):899-906. (PMID: 3924412)
    • Grant Information:
      K22CA193848 United States NH NIH HHS; K22 CA193848 United States CA NCI NIH HHS; Comprehensive Cancer Center; T32 GM150375 United States GM NIGMS NIH HHS; R01 CA269977 United States CA NCI NIH HHS; University of Chicago
    • Accession Number:
      0 (RNA, Long Noncoding)
    • Publication Date:
      Date Created: 20240725 Date Completed: 20240909 Latest Revision: 20241030
    • Publication Date:
      20241031
    • Accession Number:
      PMC11381332
    • Accession Number:
      10.1093/nar/gkae646
    • Accession Number:
      39051548