@article {Dilworth114298, author = {MP Dilworth and T Nieto and JD Stockton and C Whalley and L Tee and JD James and MT Hallissey and R Hejmadi and N Trugdill and O Tucker and AD Beggs}, title = {Whole genome methylation analysis of non-dysplastic Barretts oesophagus that progresses to invasive cancer}, elocation-id = {114298}, year = {2017}, doi = {10.1101/114298}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Objective To investigate differences in methylation between patients with non-dysplastic Barretts{\textquoteright} 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{\textquoteright}s Oesophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencingResults In total, 12 patients with {\textquotedblleft}progressive{\textquotedblright} vs. 12 with {\textquotedblleft}non-progressive{\textquotedblright} non-dysplastic Barrett{\textquoteright}s oesophagus were analysed via methylation array. Fourty-four methylation markers were identified that may be able to discriminate between non-dysplastic Barrett{\textquoteright}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{\textquoteright}s Oesophagus and may form the basis of a future surveillance program.}, URL = {https://www.biorxiv.org/content/early/2017/03/06/114298}, eprint = {https://www.biorxiv.org/content/early/2017/03/06/114298.full.pdf}, journal = {bioRxiv} }