Differential Localization of β-catenin Protein in CTNNB1 mutant Endometrial Cancers Results in Distinct Transcriptional Profiles

CTNNB1 exon 3 mutation is a well-established driver of nearly 30% of endometrioid endometrial cancers (EEC), and this is associated with worse patient survival. The purpose of this study was to determine downstream gene expression in these cancers with nuclear or membrane/cytoplasmic mutant b-catenin protein localization. We determined that EECs with exon 3 CTNNB1 mutations have variable b-catenin localization, and this is associated with profoundly distinct foci of gene expression within the same cancer. Sixteen formalin-fixed paraffin embedded tumors with exon 3 CTNNB1 mutations and heterogenous localization of b-catenin (nuclear or non-nuclear) were analyzed with spatial transcriptomics. Six regions of interest were selected per tumor, 3 with nuclear mutant b-catenin and 3 with non-nuclear mutant b-catenin.