The methylomic landscape of fallopian tube lesions associated with ovarian high grade serous carcinoma

The current paradigm in the development of high-grade serous carcinomas (HGSCs) proposes that the majority of HGSCs arise from precursor serous tubal intraepithelial carcinoma (STIC) lesions of the fallopian tube. The goal of this study is to identify genomic regions that exhibit high-specificity differential hypermethylation for potential use as biomarkers for detecting STIC and HGSC at stages when curative intervention likely remains feasible. We used MethylationEPIC platform to compare genome-wide methylation among 12 STICs along with respective adjacent-normal epithelia, one p53 signature lesion and 2 samples of concurrent HGSC. The resulting methylomic data were analyzed by unsupervised hierarchical clustering and multidimensional analysis. Regions of high-confidence STIC-specific differential hypermethylation were identified using selective bioinformatic criteria and compared with published MethylationEPIC data (GSE155760) from 23 HGSC tumors and 11 healthy fallopian tube mucosae.