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dc.contributor.authorAttolini, Camille Stephan-Otto
dc.contributor.authorCheng, Yu-Kang
dc.contributor.authorBeroukhim, Rameen
dc.contributor.authorGetz, Gad
dc.contributor.authorAbdel-Wahab, Omar
dc.contributor.authorLevine, Ross L.
dc.contributor.authorMellinghoff, Ingo K.
dc.contributor.authorMichor, Franziska
dc.date.accessioned2019-09-30T11:55:46Z
dc.date.issued2010
dc.identifier.citationAttolini, Camille Stephan-Otto, Yu-Kang Cheng, Rameen Beroukhim, Gad Getz, Omar Abdel-Wahab, Ross L. Levine, Ingo K. Mellinghoff, and Franziska Michor. 2010. “A Mathematical Framework to Determine the Temporal Sequence of Somatic Genetic Events in Cancer.” Proceedings of the National Academy of Sciences 107 (41): 17604–9. https://doi.org/10.1073/pnas.1009117107.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41426760*
dc.description.abstractHuman cancer is caused by the accumulation of genetic alterations in cells. Of special importance are changes that occur early during malignant transformation because they may result in oncogene addiction and represent promising targets for therapeutic intervention. Here we describe a computational approach, called Retracing the Evolutionary Steps in Cancer (RESIC), to deduce the temporal sequence of genetic events during tumorigenesis from cross-sectional genomic data of tumors at their fully transformed stage. When applied to a dataset of 70 advanced colorectal cancers, our algorithm accurately predicts the sequence of APC, KRAS, and TP53 mutations previously defined by analyzing tumors at different stages of colon cancer formation. We further validate the method with glioblastoma and leukemia sample data and then apply it to complex integrated genomics databases, finding that high-level EGFR amplification appears to be a late event in primary glioblastomas. RESIC represents the first evolutionary mathematical approach to identify the temporal sequence of mutations driving tumorigenesis and may be useful to guide the validation of candidate genes emerging from cancer genome surveys.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleA mathematical framework to determine the temporal sequence of somatic genetic events in cancer
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorMichor, Franziska L.::39edaa85d22807af96234c8783b91c0c::600
dc.date.available2019-09-30T11:55:46Z
dash.workflow.comments1Science Serial ID 90491
dc.identifier.doi10.1073/pnas.1009117107
dash.source.volume107;41
dash.source.page17604


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