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dc.contributor.authorNeskey, David M.
Osman, Abdullah A.
Ow, Thomas J.
Katsonis, Panagiotis
McDonald, Thomas
Hicks, Stephanie C.
Hsu, Teng-Kuei
Pickering, Curtis R.
Ward, Alexandra
Patel, Ameeta
Yordy, John S.
Skinner, Heath D.
Giri, Uma
Sano, Daisuke
Story, Michael D.
Beadle, Beth M.
El-Naggar, Adel K.
Kies, Merrill S.
William, William N.
Caulin, Carlos
Frederick, Mitchell
Kimmel, Marek
Myers, Jeffrey N.
Lichtarge, Olivier
dc.date.accessioned 2017-05-15T17:23:57Z
dc.date.available 2017-05-15T17:23:57Z
dc.date.issued 2015
dc.identifier.citation Neskey, 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." Cancer Research, 75, no. 7 (2015) AACR: 1527-1536. http://dx.doi.org/10.1158/0008-5472.CAN-14-2735.
dc.identifier.urihttps://hdl.handle.net/1911/94254
dc.description.abstract TP53 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.
dc.language.iso eng
dc.publisher AACR
dc.rights This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by AACR.
dc.title Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer
dc.type Journal article
dc.citation.journalTitle Cancer Research
dc.citation.volumeNumber 75
dc.citation.issueNumber 7
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.CAN-14-2735
dc.identifier.pmcid PMC4383697
dc.identifier.pmid 25634208
dc.type.publication post-print
dc.citation.firstpage 1527
dc.citation.lastpage 1536


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