Whole genome methylation analysis of non-dysplastic Barretts oesophagus that progresses to invasive cancer

Objective: To investigate differences in methylation between patients with nondysplastic Barretts’ oesophagus who progress to invasive adenocarcinoma and those that do not. Design: A whole genome methylation interrogation using the Illumina HumanMethylation 450 array of patients with non-dysplastic Barrett’s Oesophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencing Results: In total, 12 patients with “progressive” vs. 12 with “non-progressive” nondysplastic Barrett’s oesophagus were analysed via methylation array. Fourty-four methylation markers were identified that may be able to discriminate between nondysplastic Barrett’s Oesophagus that either progress to adenocarcinoma or remain static. Hypomethylation of the recently identified tumour supressor OR3A4 (probe cg09890332) validated in a separate cohort of samples (median methylation in progressors = 67.8% vs. 96.7% in non-progressors,p=0.0001, z = 3.85, Wilcoxon rank sum test) and was associated with the progression to adenocarcinoma. There were no differences in copy number between the two groups, but a global trend towards hypomethylation in the progressor group was observed. Conclusion: Hypomethylation of OR3A4 has the ability to risk stratify the patient with non-dysplastic Barrett’s Oesophagus and may form the basis of a future surveillance program. . CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/114298 doi: bioRxiv preprint first posted online Mar. 6, 2017;