The methylomic landscape of fallopian tube lesions associated with ovarian high grade serous carcinoma. 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. Overall design: 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.

高级别浆液性癌（high-grade serous carcinomas, HGSCs）的现有研究范式认为，绝大多数HGSC起源于输卵管的浆液性输卵管上皮内癌（serous tubal intraepithelial carcinoma, STIC）前驱病变。本研究旨在鉴定具备高特异性差异高甲基化特征的基因组区域，以作为生物标志物，在可实施治愈性干预的阶段实现STIC与HGSC的早期检测。总体实验设计：本研究采用MethylationEPIC平台，对12例STIC样本及其配对癌旁正常上皮、1例p53标记性病变以及2例同步并发HGSC样本开展全基因组甲基化水平对比分析。所得甲基化组数据通过无监督层级聚类与多维分析进行处理；通过选择性生物信息学筛选标准鉴定出高置信度的STIC特异性差异高甲基化区域，并与已发表的GSE155760数据集的MethylationEPIC数据进行比对，该数据集包含23例HGSC肿瘤组织与11例健康输卵管黏膜样本。