Global analysis of epigenetic heterogeneity identifies divergent drivers of esophageal squamous cell carcinoma

CAO, W.; Lee, H.; Wu, W.; Zaman, A.; McCorkle, S.; Yan, M.; Chen, J.; Xing, Q.; Sinnott-Armstrong, N.; Xu, H.; Sailani, M. R.; Tang, W.; Cui, Y.; Liu, J.; Guan, H.; Lv, P.; Sun, X.; Sun, L.; Han, P.; Lou, Y.; Chang, J.; Wang, J.; Gao, Y.; Guo, J.; Schenk, G.; Shain, A. H.; Biddle, F. G.; Collisson, E.; Snyder, M.; Bivona, T. G.

doi:10.1101/641357

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bioRxiv · 10.1101/641357

Global analysis of epigenetic heterogeneity identifies divergent drivers of esophageal squamous cell carcinoma

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Abstract

Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome and two-thirds occur in long non-coding (lnc)RNA regions. DNA methylation and epigenetic heterogeneity both coincide with chromosomal topological alterations. Gene body methylation, polycomb repressive complex occupancy, and CTCF binding sites associate with cancer-specific gene regulation. Epigenetically-mediated activation of non-canonical WNT signaling and the lncRNA ESCCAL-1 were validated as potential ESCC driver alterations. Gene-specific cancer driver roles of epigenetic alterations and heterogeneity are identified.

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CAO, W., Lee, H., Wu, W., Zaman, A., McCorkle, S., Yan, M., Chen, J., Xing, Q., Sinnott-Armstrong, N., Xu, H., Sailani, M. R., Tang, W., Cui, Y., Liu, J., Guan, H., Lv, P., Sun, X., Sun, L., Han, P., Lou, Y., Chang, J., Wang, J., Gao, Y., Guo, J., Schenk, G., Shain, A. H., Biddle, F. G., Collisson, E., Snyder, M., Bivona, T. G.. 2019-05-18. Global analysis of epigenetic heterogeneity identifies divergent drivers of esophageal squamous cell carcinoma. https://doi.org/10.1101/641357

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