dc.contributor.author | Hnisz, D. | |
dc.contributor.author | Day, D. S. | |
dc.contributor.author | Valton, A.-L. | |
dc.contributor.author | Bak, R. O. | |
dc.contributor.author | Goldmann, J. | |
dc.contributor.author | Lajoie, B. R. | |
dc.contributor.author | Sigova, A. A. | |
dc.contributor.author | Lee, T. I. | |
dc.contributor.author | Porteus, M. H. | |
dc.contributor.author | Dekker, J. | |
dc.contributor.author | Weintraub, Abraham Selby | |
dc.contributor.author | Li, Charles Han | |
dc.contributor.author | Reddy, Jessica | |
dc.contributor.author | Borges-Rivera, Diego Ramon | |
dc.contributor.author | Jaenisch, Rudolf | |
dc.contributor.author | Fan, Zi Peng | |
dc.contributor.author | Young, Richard A. | |
dc.date.accessioned | 2017-01-24T21:30:49Z | |
dc.date.available | 2017-01-24T21:30:49Z | |
dc.date.issued | 2015-11 | |
dc.date.submitted | 2016-03 | |
dc.identifier.issn | 0036-8075 | |
dc.identifier.issn | 1095-9203 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/106605 | |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grants HG002668, CA109901, NS088538, and MH104610) | en_US |
dc.description.sponsorship | Virginia and Daniel K. Ludwig Graduate Fellowship | en_US |
dc.language.iso | en_US | |
dc.publisher | American Association for the Advancement of Science (AAAS) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1126/science.aad9024 | en_US |
dc.rights | 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. | en_US |
dc.source | PMC | en_US |
dc.title | Activation of proto-oncogenes by disruption of chromosome neighborhoods | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Hnisz, D. et al. “Activation of Proto-Oncogenes by Disruption of Chromosome Neighborhoods.” Science 351.6280 (2016): 1454–1458. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Computational and Systems Biology Program | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.mitauthor | Weintraub, Abraham Selby | |
dc.contributor.mitauthor | Li, Charles Han | |
dc.contributor.mitauthor | Reddy, Jessica | |
dc.contributor.mitauthor | Borges-Rivera, Diego Ramon | |
dc.contributor.mitauthor | Jaenisch, Rudolf | |
dc.contributor.mitauthor | Fan, Zi Peng | |
dc.contributor.mitauthor | Young, Richard A | |
dc.relation.journal | Science | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Hnisz, D.; Weintraub, A. S.; Day, D. S.; Valton, A.-L.; Bak, R. O.; Li, C. H.; Goldmann, J.; Lajoie, B. R.; Fan, Z. P.; Sigova, A. A.; Reddy, J.; Borges-Rivera, D.; Lee, T. I.; Jaenisch, R.; Porteus, M. H.; Dekker, J.; Young, R. A. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-0998-9882 | |
dc.identifier.orcid | https://orcid.org/0000-0001-8091-6112 | |
dc.identifier.orcid | https://orcid.org/0000-0002-2171-9394 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1650-2289 | |
dc.identifier.orcid | https://orcid.org/0000-0001-8855-8647 | |
mit.license | PUBLISHER_POLICY | en_US |