Abstract 431: CYP26C1 gene is highly methylated and correlated with chemoradiation therapy in esophageal squamous cell carcinoma

Background: Systemic chemo- and chemoradiation- therapy is widely accepted in esophageal squamous cell carcinoma (ESCC) patients. However resistance to these therapies remaining pretty high and multicentric occurrence of ESCC often can see after treatment. Multiple studies have shown that promoter methylation of tumor suppressor genes underlie esophageal carcinogenesis. But, we still do not know that epigenetic changes after chemoradiation therapy (CRT) in ESCC. Our aim is to identify how change DNA methylation in tumor site (T) but also adjacent normal site (ADJ) before/after CRT. Methods: Tumor and adjacent normal biopsy specimens were obtained before/after treatment from 34 patients (124 samples) enrolled in a uniform CRT protocol. Genomewide DNA methylation analysis was performed using 12 non-treated test samples (T and matched ADJ: 6 each) by methylated CpG island amplification and microarray (MCAM) method (4x44K, Agilent custom array), and selected candidate genes that were highly methylated in T than ADJ. We next analyzed one of the candidate genes CYP26C1 (cytochrome P450, family 26, subfamily C, polypeptide 1) DNA methylation using 112 validation samples by quantitative bisulfate pyrosequencing. Results: CYP26C1 was selected by unsupervised hierarchical clustering after MCAM in test samples. CYP26C1 DNA methylation was significantly high in T than ADJ in both test and validation samples (p