Abstract
Abstract Human papillomavirus-related head and neck squamous cell carcinoma (HPV+ HNSCC) is characterized by abundant gene expression changes, which cannot be explained by limited genetic alterations alone. We hypothesized that epigenetically regulated super-enhancers (SEs) are the drivers of aberrant gene expression in HPV+ HNSCC. We used integrated analysis of DNA methylation and gene expression data for cancer and noncancer oropharyngeal tissues to discover actionable SEs that regulate expression of target genes in HPV+ HNSCC. Since no SEs are currently defined for any HNSCC samples; we investigated 6196 SE elements that were obtained from the public domain for closely related tissues, including normal and tumor lung, and cervical cancer cell lines. We analyzed the methylation of these elements and gene expression of their nearby genes for 47 HPV+ HNSCC and their 25 noncancer controls. Overall, we found 122 differentially methylated SEs that had putative target (nearby) genes whose expression was correlated with enhancer methylation in HPV+ HNSCC. Of these, 107 were hypermethylated, and 15 were hypomethylated in tumors relative to normal samples. The pathway analysis revealed that the inferred SE-regulated genes were associated with pathways known to regulate carcinogenesis. Our data demonstrate that gene expression in HPV+ HNSCC may be regulated by epigenetic alterations in SE elements of related tissues. Citation Format: Emily L. Flam, Dylan Z. Kelley, Elena Stavrovskaya, Ludmila Danilova, Theresa Guo, Michael Considine, Jiang Qian, Joseph A. Califano, Alexander V. Favorov, Elana J. Fertig, Daria A. Gaykalova. Differentially methylated super-enhancers regulate gene expression in human papillomavirus-related head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 364.
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