Functional analysis of somatic variants found in endometrial tumor-specific ER-alpha enhancers

Biological implications of healthy- and tumor-specific ERα cistromes in endometrial tumors have largely been understudied. Moreover, the functional impact of non-coding somatic variants has commonly been underexplored and remained elusive. This study is aimed to provide functional interpretation of non-coding somatic variants associated with tumor-specific ERα cistrome. Integrating the ChIP-seq analyses with the whole genome sequencing from the set of metastatic endometrial tumors and matched controls we observed that tumor-specific ERα cistrome is enriched for somatic variants. Additionally, H3K27Ac Hi-ChIP in cancer cell lines identified potential target genes of tumor-specific enhancers and coincident variants. We aim to employ CRISPR to identify tumor-specific ERα enhancers and target genes critical for estrogen-driven proliferation of endometrial cancer-cell lines. Through multidimensional omics data integration, our study is specifically geared to shed new lights on the molecular mechanisms of endometrial cancer development and progression and the functional impact of non-coding somatic mutations.