Small genomic insertions form enhancers that misregulate oncogenes
The non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challeng...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/110068 https://orcid.org/0000-0003-0998-9882 https://orcid.org/0000-0001-8091-6112 https://orcid.org/0000-0001-8855-8647 |
| _version_ | 1826213821667082240 |
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| author | Hnisz, Denes Li, Zhaodong Weichert-Leahey, Nina Rahman, Sunniyat Liu, Yu Etchin, Julia Li, Benshang Shen, Shuhong Zhang, Jinghui Look, A. Thomas Mansour, Marc R. Abraham, Brian Joseph Weintraub, Abraham Selby Kwiatkowski, Nick Li, Charles Han Lee, Tong Ihn Young, Richard A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Hnisz, Denes Li, Zhaodong Weichert-Leahey, Nina Rahman, Sunniyat Liu, Yu Etchin, Julia Li, Benshang Shen, Shuhong Zhang, Jinghui Look, A. Thomas Mansour, Marc R. Abraham, Brian Joseph Weintraub, Abraham Selby Kwiatkowski, Nick Li, Charles Han Lee, Tong Ihn Young, Richard A. |
| author_sort | Hnisz, Denes |
| collection | MIT |
| description | The non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants. Among the 102 tumour cell genomes we analyse, small insertions are frequently observed in enhancer DNA sequences near known oncogenes. Further study of one insertion, somatically acquired in primary leukaemia tumour genomes, reveals that it nucleates formation of an active enhancer that drives expression of the LMO2 oncogene. The approach described here to identify enhancer-associated small insertion variants provides a foundation for further study of these abnormalities across human cancers. |
| first_indexed | 2024-09-23T15:55:22Z |
| format | Article |
| id | mit-1721.1/110068 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:55:22Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1100682022-10-02T05:06:15Z Small genomic insertions form enhancers that misregulate oncogenes Hnisz, Denes Li, Zhaodong Weichert-Leahey, Nina Rahman, Sunniyat Liu, Yu Etchin, Julia Li, Benshang Shen, Shuhong Zhang, Jinghui Look, A. Thomas Mansour, Marc R. Abraham, Brian Joseph Weintraub, Abraham Selby Kwiatkowski, Nick Li, Charles Han Lee, Tong Ihn Young, Richard A. Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Abraham, Brian Joseph Weintraub, Abraham Selby Kwiatkowski, Nick Li, Charles Han Lee, Tong Ihn Young, Richard A The non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants. Among the 102 tumour cell genomes we analyse, small insertions are frequently observed in enhancer DNA sequences near known oncogenes. Further study of one insertion, somatically acquired in primary leukaemia tumour genomes, reveals that it nucleates formation of an active enhancer that drives expression of the LMO2 oncogene. The approach described here to identify enhancer-associated small insertion variants provides a foundation for further study of these abnormalities across human cancers. United States. National Institutes of Health (HG002668) United States. National Institutes of Health (CA109901) 2017-06-20T17:39:19Z 2017-06-20T17:39:19Z 2017-06-20 2016-01 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/110068 Abraham, Brian J.; Hnisz, Denes; Weintraub, Abraham S.; Kwiatkowski, Nicholas; Li, Charles H.; Li, Zhaodong; Weichert-Leahey, Nina et al. “Small Genomic Insertions Form Enhancers That Misregulate Oncogenes.” Nature Communications 8 (February 2017): 14385 © The Author(s) 2017 https://orcid.org/0000-0003-0998-9882 https://orcid.org/0000-0001-8091-6112 https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1038/ncomms14385 Nature Communications Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Hnisz, Denes Li, Zhaodong Weichert-Leahey, Nina Rahman, Sunniyat Liu, Yu Etchin, Julia Li, Benshang Shen, Shuhong Zhang, Jinghui Look, A. Thomas Mansour, Marc R. Abraham, Brian Joseph Weintraub, Abraham Selby Kwiatkowski, Nick Li, Charles Han Lee, Tong Ihn Young, Richard A. Small genomic insertions form enhancers that misregulate oncogenes |
| title | Small genomic insertions form enhancers that misregulate oncogenes |
| title_full | Small genomic insertions form enhancers that misregulate oncogenes |
| title_fullStr | Small genomic insertions form enhancers that misregulate oncogenes |
| title_full_unstemmed | Small genomic insertions form enhancers that misregulate oncogenes |
| title_short | Small genomic insertions form enhancers that misregulate oncogenes |
| title_sort | small genomic insertions form enhancers that misregulate oncogenes |
| url | http://hdl.handle.net/1721.1/110068 https://orcid.org/0000-0003-0998-9882 https://orcid.org/0000-0001-8091-6112 https://orcid.org/0000-0001-8855-8647 |
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