Acetylated Histone H4K16 is Predictive of the Biology of Esophageal Adenocarcinoma

Puja G. Khaitan ¹, Tej Pandita ²

¹ Medstar Washington Hospital Center, Washington DC, USA; ² Houston Methodist Hospital, Houston, USA;

Date, time and location: 2018.05.26 17:00, Congress Hall, 2F–C

Abstract

Background: The incidence of gastro-esophageal disease and associated rate of esophageal adenocarcinoma (EAC) is rising at an exponential rate. However, research targeting EAC is lagging behind, and much research is needed in the field to identify ways to diagnose EAC early and to improve the rate of pathologic complete response (pCR) to chemoradiation. We wanted to understand DNA repair pathways and potential targets that could sensitize EAC tumors and yield higher pCR rates, as that would result in improved patient survival and decreased metastatic potential. Acetylated H4 on lysine 16 residue (H4K16) is known to play a role in routine cellular processes and DNA repair, in both homologous recombination and non-homologous end joining. Dysregulated H4K16Ac levels, indeed, have been associated with different solid malignancies. Hypothesis: H4K16Ac levels, as regulated by MOF, may play a role in EAC and its resistance to radiation. Methods: After establishing baseline levels of MOF and H4K16Ac in normal tissue, we determined H4K16Ac levels in esophageal tumors and compared the levels between those tumors that responded to neoadjuvant chemoradiation versus those that did not. Results: Lower H4K16Ac levels correlated with tumors that responded well to chemoradiation. This confirmed that epigenetic modification of a histone protein in EAC leads to enhanced DNA repair, thus resulting in increased resistance of tumor to chemoradiation. Conclusions: H4K16Ac levels are predictive of tumor response to radiation therapy. Higher H4K16Ac levels correlate with enhanced DNA repair mechanisms and therefore, development of radiation-resistance. This in turn would make H4K16Ac level become a biomarker to predict tumor response to chemoradiation.