Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer

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dc.citation.firstpage1527en_US
dc.citation.issueNumber7en_US
dc.citation.journalTitleCancer Researchen_US
dc.citation.lastpage1536en_US
dc.citation.volumeNumber75en_US
dc.contributor.authorNeskey, David M.en_US
dc.contributor.authorOsman, Abdullah A.en_US
dc.contributor.authorOw, Thomas J.en_US
dc.contributor.authorKatsonis, Panagiotisen_US
dc.contributor.authorMcDonald, Thomasen_US
dc.contributor.authorHicks, Stephanie C.en_US
dc.contributor.authorHsu, Teng-Kueien_US
dc.contributor.authorPickering, Curtis R.en_US
dc.contributor.authorWard, Alexandraen_US
dc.contributor.authorPatel, Ameetaen_US
dc.contributor.authorYordy, John S.en_US
dc.contributor.authorSkinner, Heath D.en_US
dc.contributor.authorGiri, Umaen_US
dc.contributor.authorSano, Daisukeen_US
dc.contributor.authorStory, Michael D.en_US
dc.contributor.authorBeadle, Beth M.en_US
dc.contributor.authorEl-Naggar, Adel K.en_US
dc.contributor.authorKies, Merrill S.en_US
dc.contributor.authorWilliam, William N.en_US
dc.contributor.authorCaulin, Carlosen_US
dc.contributor.authorFrederick, Mitchellen_US
dc.contributor.authorKimmel, Mareken_US
dc.contributor.authorMyers, Jeffrey N.en_US
dc.contributor.authorLichtarge, Olivieren_US
dc.date.accessioned2017-05-15T17:23:57Zen_US
dc.date.available2017-05-15T17:23:57Zen_US
dc.date.issued2015en_US
dc.description.abstractTP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive. In the current study, we evaluated a novel computational approach termed evolutionary action (EAp53) to stratify patients with tumors harboring TP53 mutations as high or low risk, and validated this system in both in vivo and in vitro models. Patients with high-risk TP53 mutations had the poorest survival outcomes and the shortest time to the development of distant metastases. Tumor cells expressing high-risk TP53 mutations were more invasive and tumorigenic and they exhibited a higher incidence of lung metastases. We also documented an association between the presence of high-risk mutations and decreased expression of TP53 target genes, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior. Overall, our work validated EAp53 as a novel computational tool that may be useful in clinical prognosis of tumors harboring p53 mutations.en_US
dc.identifier.citationNeskey, David M., Osman, Abdullah A., Ow, Thomas J., et al.. "Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer." <i>Cancer Research,</i> 75, no. 7 (2015) AACR: 1527-1536. http://dx.doi.org/10.1158/0008-5472.CAN-14-2735.en_US
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.CAN-14-2735en_US
dc.identifier.urihttps://hdl.handle.net/1911/94254en_US
dc.language.isoengen_US
dc.publisherAACRen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by AACR.en_US
dc.titleEvolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Canceren_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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