dc.contributor.author | Wang, Guangchuan | |
dc.contributor.author | Chow, Ryan D. | |
dc.contributor.author | Ye, Lupeng | |
dc.contributor.author | Guzman, Christopher D. | |
dc.contributor.author | Dai, Xiaoyun | |
dc.contributor.author | Dong, Matthew B. | |
dc.contributor.author | Zhang, Feng | |
dc.contributor.author | Platt, Randall Jeffrey | |
dc.contributor.author | Chen, Sidi | |
dc.contributor.author | Sharp, Phillip A. | |
dc.date.accessioned | 2018-10-11T14:38:33Z | |
dc.date.available | 2018-10-11T14:38:33Z | |
dc.date.issued | 2018-02 | |
dc.date.submitted | 2017-08 | |
dc.identifier.issn | 2375-2548 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/118426 | |
dc.description.abstract | Cancer genomics consortia have charted the landscapes of numerous human cancers. Whereas somemutations were found in classical oncogenes and tumor suppressors, others have not yet been functionally studied in vivo. To date, a comprehensive assessment of how these genes influence oncogenesis is lacking. We performed direct highthroughput in vivo mapping of functional variants in an autochthonous mouse model of cancer. Using adenoassociated viruses (AAVs) carrying a single-guide RNA (sgRNA) library targeting putative tumor suppressor genes significantly mutated in human cancers, we directly pool-mutagenized the livers of Cre-inducible CRISPR (clustered regularly interspaced short palindromic repeats)-associated protein 9 (Cas9) mice. All mice that received the AAV-mTSG library developed liver cancer and diedwithin 4 months.We usedmolecular inversion probe sequencing of the sgRNA target sites to chart the mutational landscape of these tumors, revealing the functional consequence of multiple variants in driving liver tumorigenesis in immunocompetent mice. AAV-mediated autochthonous CRISPR screens provide a powerful means for mapping a provisional functional cancer genome atlas of tumor suppressors in vivo. | en_US |
dc.description.sponsorship | Damon Runyon Cancer Research Foundation (DRG-2117-12; DFS-13-15) | en_US |
dc.description.sponsorship | Melanoma Research Foundation (412806, 16-003524) | en_US |
dc.description.sponsorship | St. Baldrick’s Foundation (426685) | en_US |
dc.description.sponsorship | American Cancer Society (IRG 58-012-54) | en_US |
dc.description.sponsorship | Cancer Research Institute (New York, N.Y.) | en_US |
dc.description.sponsorship | Breast Cancer Alliance | en_US |
dc.description.sponsorship | Cancer Research Institute (New York, N.Y.) (Clinic and Laboratory Integration Program) | en_US |
dc.description.sponsorship | American Association for Cancer Research (499395) | en_US |
dc.description.sponsorship | United States. Department of Defense (W81XWH-17-1-0235) | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) (1U54CA209992) | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) (5P50CA196530-A10805) | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) (4P50CA121974-A08306) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (R01-CA133404) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (R01-GM034277) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (CCNE) | en_US |
dc.description.sponsorship | Skolkovo Foundation | en_US |
dc.description.sponsorship | Casimir-Lambert Fund | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (grant 1R01-HG009761) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (grant R01-MH110049) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (grant DP1-HL141201) | en_US |
dc.description.sponsorship | Howard Hughes Medical Institute | en_US |
dc.description.sponsorship | New York Stem Cell Foundation | en_US |
dc.description.sponsorship | Simons, Paul G. Allen Family | en_US |
dc.description.sponsorship | Vallee Foundations | en_US |
dc.description.sponsorship | Poitras Center for Affective Disorders Research at MIT | en_US |
dc.description.sponsorship | Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT | en_US |
dc.publisher | American Association for the Advancement of Science (AAAS) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1126/SCIADV.AAO5508 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial 4.0 International | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | en_US |
dc.source | Science Advances | en_US |
dc.title | Mapping a functional cancer genome atlas of tumor suppressors in mouse liver using AAV-CRISPR–mediated direct in vivo screening | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Wang, Guangchuan, Ryan D. Chow, Lupeng Ye, Christopher D. Guzman, Xiaoyun Dai, Matthew B. Dong, Feng Zhang, Phillip A. Sharp, Randall J. Platt, and Sidi Chen. “Mapping a Functional Cancer Genome Atlas of Tumor Suppressors in Mouse Liver Using AAV-CRISPR–mediated Direct in Vivo Screening.” Science Advances 4, no. 2 (February 2018): eaao5508. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences | en_US |
dc.contributor.department | McGovern Institute for Brain Research at MIT | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Zhang, Feng | |
dc.contributor.mitauthor | Sharp, Phillip A | |
dc.contributor.mitauthor | Platt, Randall Jeffrey | |
dc.contributor.mitauthor | Chen, Sidi | |
dc.relation.journal | Science Advances | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2018-10-10T16:12:45Z | |
dspace.orderedauthors | Wang, Guangchuan; Chow, Ryan D.; Ye, Lupeng; Guzman, Christopher D.; Dai, Xiaoyun; Dong, Matthew B.; Zhang, Feng; Sharp, Phillip A.; Platt, Randall J.; Chen, Sidi | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-2782-2509 | |
dc.identifier.orcid | https://orcid.org/0000-0003-1465-1691 | |
mit.license | PUBLISHER_CC | en_US |