Activation of proto-oncogenes by disruption of chromosome neighborhoods
Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur wit...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Association for the Advancement of Science (AAAS)
2017
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| Online Access: | http://hdl.handle.net/1721.1/106605 https://orcid.org/0000-0003-0998-9882 https://orcid.org/0000-0001-8091-6112 https://orcid.org/0000-0002-2171-9394 https://orcid.org/0000-0002-1650-2289 https://orcid.org/0000-0001-8855-8647 |
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| author | Hnisz, D. Day, D. S. Valton, A.-L. Bak, R. O. Goldmann, J. Lajoie, B. R. Sigova, A. A. Lee, T. I. Porteus, M. H. Dekker, J. Weintraub, Abraham Selby Li, Charles Han Reddy, Jessica Borges-Rivera, Diego Ramon Jaenisch, Rudolf Fan, Zi Peng Young, Richard A. |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Hnisz, D. Day, D. S. Valton, A.-L. Bak, R. O. Goldmann, J. Lajoie, B. R. Sigova, A. A. Lee, T. I. Porteus, M. H. Dekker, J. Weintraub, Abraham Selby Li, Charles Han Reddy, Jessica Borges-Rivera, Diego Ramon Jaenisch, Rudolf Fan, Zi Peng Young, Richard A. |
| author_sort | Hnisz, D. |
| collection | MIT |
| description | Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these structures and whether oncogene activation can occur via disruption of insulated neighborhood boundaries in cancer cells. We mapped insulated neighborhoods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurrent microdeletions that eliminate the boundary sites of insulated neighborhoods containing prominent T-ALL proto-oncogenes. Perturbation of such boundaries in nonmalignant cells was sufficient to activate proto-oncogenes. Mutations affecting chromosome neighborhood boundaries were found in many types of cancer. Thus, oncogene activation can occur via genetic alterations that disrupt insulated neighborhoods in malignant cells. |
| first_indexed | 2024-09-23T10:23:09Z |
| format | Article |
| id | mit-1721.1/106605 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:23:09Z |
| publishDate | 2017 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1066052022-09-26T17:33:40Z Activation of proto-oncogenes by disruption of chromosome neighborhoods Hnisz, D. Day, D. S. Valton, A.-L. Bak, R. O. Goldmann, J. Lajoie, B. R. Sigova, A. A. Lee, T. I. Porteus, M. H. Dekker, J. Weintraub, Abraham Selby Li, Charles Han Reddy, Jessica Borges-Rivera, Diego Ramon Jaenisch, Rudolf Fan, Zi Peng Young, Richard A. Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Weintraub, Abraham Selby Li, Charles Han Reddy, Jessica Borges-Rivera, Diego Ramon Jaenisch, Rudolf Fan, Zi Peng Young, Richard A Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control of key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these structures and whether oncogene activation can occur via disruption of insulated neighborhood boundaries in cancer cells. We mapped insulated neighborhoods in T cell acute lymphoblastic leukemia (T-ALL) and found that tumor cell genomes contain recurrent microdeletions that eliminate the boundary sites of insulated neighborhoods containing prominent T-ALL proto-oncogenes. Perturbation of such boundaries in nonmalignant cells was sufficient to activate proto-oncogenes. Mutations affecting chromosome neighborhood boundaries were found in many types of cancer. Thus, oncogene activation can occur via genetic alterations that disrupt insulated neighborhoods in malignant cells. National Institutes of Health (U.S.) (Grants HG002668, CA109901, NS088538, and MH104610) Virginia and Daniel K. Ludwig Graduate Fellowship 2017-01-24T21:30:49Z 2017-01-24T21:30:49Z 2015-11 2016-03 Article http://purl.org/eprint/type/JournalArticle 0036-8075 1095-9203 http://hdl.handle.net/1721.1/106605 Hnisz, D. et al. “Activation of Proto-Oncogenes by Disruption of Chromosome Neighborhoods.” Science 351.6280 (2016): 1454–1458. https://orcid.org/0000-0003-0998-9882 https://orcid.org/0000-0001-8091-6112 https://orcid.org/0000-0002-2171-9394 https://orcid.org/0000-0002-1650-2289 https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1126/science.aad9024 Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Hnisz, D. Day, D. S. Valton, A.-L. Bak, R. O. Goldmann, J. Lajoie, B. R. Sigova, A. A. Lee, T. I. Porteus, M. H. Dekker, J. Weintraub, Abraham Selby Li, Charles Han Reddy, Jessica Borges-Rivera, Diego Ramon Jaenisch, Rudolf Fan, Zi Peng Young, Richard A. Activation of proto-oncogenes by disruption of chromosome neighborhoods |
| title | Activation of proto-oncogenes by disruption of chromosome neighborhoods |
| title_full | Activation of proto-oncogenes by disruption of chromosome neighborhoods |
| title_fullStr | Activation of proto-oncogenes by disruption of chromosome neighborhoods |
| title_full_unstemmed | Activation of proto-oncogenes by disruption of chromosome neighborhoods |
| title_short | Activation of proto-oncogenes by disruption of chromosome neighborhoods |
| title_sort | activation of proto oncogenes by disruption of chromosome neighborhoods |
| url | http://hdl.handle.net/1721.1/106605 https://orcid.org/0000-0003-0998-9882 https://orcid.org/0000-0001-8091-6112 https://orcid.org/0000-0002-2171-9394 https://orcid.org/0000-0002-1650-2289 https://orcid.org/0000-0001-8855-8647 |
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