dc.contributor.author | Adalsteinsson, Viktor A. | |
dc.contributor.author | Tallapragada, Naren | |
dc.contributor.author | Tahirova, Narmin | |
dc.contributor.author | Regev, Aviv | |
dc.contributor.author | Love, John C | |
dc.date.accessioned | 2014-11-07T14:37:43Z | |
dc.date.available | 2014-11-07T14:37:43Z | |
dc.date.issued | 2014-04 | |
dc.date.submitted | 2013-10 | |
dc.identifier.issn | 1087-0156 | |
dc.identifier.issn | 1546-1696 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/91488 | |
dc.description.abstract | Comprehensive analyses of cancer genomes promise to inform prognoses and precise cancer treatments. A major barrier, however, is inaccessibility of metastatic tissue. A potential solution is to characterize circulating tumor cells (CTCs), but this requires overcoming the challenges of isolating rare cells and sequencing low-input material. Here we report an integrated process to isolate, qualify and sequence whole exomes of CTCs with high fidelity using a census-based sequencing strategy. Power calculations suggest that mapping of >99.995% of the standard exome is possible in CTCs. We validated our process in two patients with prostate cancer, including one for whom we sequenced CTCs, a lymph node metastasis and nine cores of the primary tumor. Fifty-one of 73 CTC mutations (70%) were present in matched tissue. Moreover, we identified 10 early trunk and 56 metastatic trunk mutations in the non-CTC tumor samples and found 90% and 73% of these mutations, respectively, in CTC exomes. This study establishes a foundation for CTC genomics in the clinic. | en_US |
dc.description.sponsorship | National Science Foundation (U.S.). Graduate Research Fellowship | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051) | en_US |
dc.description.sponsorship | Janssen Pharmaceutical Ltd. | en_US |
dc.description.sponsorship | Klarman Family Foundation | en_US |
dc.language.iso | en_US | |
dc.publisher | Nature Publishing Group | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1038/nbt.2892 | 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 | Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Lohr, Jens G, Viktor A Adalsteinsson, Kristian Cibulskis, Atish D Choudhury, Mara Rosenberg, Peter Cruz-Gordillo, Joshua M Francis, et al. “Whole-Exome Sequencing of Circulating Tumor Cells Provides a Window into Metastatic Prostate Cancer.” Nature Biotechnology 32, no. 5 (April 20, 2014): 479–484. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemical Engineering | en_US |
dc.contributor.department | Ragon Institute of MGH, MIT and Harvard | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Adalsteinsson, Viktor A. | en_US |
dc.contributor.mitauthor | Tallapragada, Naren | en_US |
dc.contributor.mitauthor | Tahirova, Narmin | en_US |
dc.contributor.mitauthor | Love, J. Christopher | en_US |
dc.contributor.mitauthor | Regev, Aviv | en_US |
dc.relation.journal | Nature Biotechnology | 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 | Lohr, Jens G; Adalsteinsson, Viktor A; Cibulskis, Kristian; Choudhury, Atish D; Rosenberg, Mara; Cruz-Gordillo, Peter; Francis, Joshua M; Zhang, Cheng-Zhong; Shalek, Alex K; Satija, Rahul; Trombetta, John J; Lu, Diana; Tallapragada, Naren; Tahirova, Narmin; Kim, Sora; Blumenstiel, Brendan; Sougnez, Carrie; Lowe, Alarice; Wong, Bang; Auclair, Daniel; Van Allen, Eliezer M; Nakabayashi, Mari; Lis, Rosina T; Lee, Gwo-Shu M; Li, Tiantian; Chabot, Matthew S; Ly, Amy; Taplin, Mary-Ellen; Clancy, Thomas E; Loda, Massimo; Regev, Aviv; Meyerson, Matthew; Hahn, William C; Kantoff, Philip W; Golub, Todd R; Getz, Gad; Boehm, Jesse S; Love, J Christopher | en_US |
dc.identifier.orcid | https://orcid.org/0000-0003-4555-2485 | |
dc.identifier.orcid | https://orcid.org/0000-0003-0921-3144 | |
dc.identifier.orcid | https://orcid.org/0000-0001-8567-2049 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |