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dc.contributor.authorOchs, Michael F.
dc.contributor.authorFertig, Elana J.
dc.contributor.authorMarkovic, Ana
dc.contributor.authorDanilova, Ludmila V.
dc.contributor.authorGaykalova, Daria A.
dc.contributor.authorCope, Leslie
dc.contributor.authorChung, Christine H.
dc.contributor.authorCalifano, Joseph A.
dc.date.accessioned2018-04-22T14:50:58Z
dc.date.available2018-04-22T14:50:58Z
dc.date.issued2013
dc.identifier.citationFertig, E. J., Markovic, A., Danilova, L. V., Gaykalova, D. A., Cope, L., Chung, C. H., & ... Califano, J. A. (2013). Preferential Activation of the Hedgehog Pathway by Epigenetic Modulations in HPV Negative HNSCC Identified with Meta-Pathway Analysis. Plos ONE, 8(11), 1-9.en_US
dc.identifier.urihttps://dx.doi.org/10.1371/journal.pone.0078127
dc.description.abstractHead and neck squamous cell carcinoma (HNSCC) is largely divided into two groups based on their etiology, human papillomavirus (HPV)-positive and –negative. Global DNA methylation changes are known to drive oncogene and tumor suppressor expression in primary HNSCC of both types. However, significant heterogeneity in DNA methylation within the groups results in different transcriptional profiles and clinical outcomes. We applied a meta-pathway analysis to link gene expression changes to DNA methylation in distinguishing HNSCC subtypes. This approach isolated specific epigenetic changes controlling expression in HPV− HNSCC that distinguish it from HPV+ HNSCC. Analysis of genes identified Hedgehog pathway activation specific to HPV− HNSCC. We confirmed that GLI1, the primary Hedgehog target, showed higher expression in tumors compared to normal samples with HPV− tumors having the highest GLI1 expression, suggesting that increased expression of GLI1 is a potential driver in HPV− HNSCC. Our algorithm for integration of DNA methylation and gene expression can infer biologically significant molecular pathways that may be exploited as therapeutics targets. Our results suggest that therapeutics targeting the Hedgehog pathway may be of benefit in HPV− HNSCC. Similar integrative analysis of high-throughput coupled DNA methylation and expression datasets may yield novel insights into deregulated pathways in other cancers.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.titlePreferential Activation of the Hedgehog Pathway by Epigenetic Modulations in HPV Negative HNSCC Identified with Meta-Pathway Analysisen_US
dc.typeArticleen_US
dc.typeTexten_US
prism.publicationNamePLOS ONE
prism.volume8
prism.issueIdentifier11
prism.publicationDate2013
dc.identifier.handlehttps://dr.tcnj.edu/handle/2900/2291


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