Integrated Methylation and Spatial Transcriptomic Profiling of Metaplastic Breast Cancer identifies putative master regulators of intratumoral heterogeneity

Metaplastic breast cancer (MpBC) is a rare and aggressive form of breast cancer. Characteristically heterogeneous, MpBC are defined by the presence of various morphological elements, typically biphasic, with epithelial (e.g. non-special type (NST), squamous) and mesenchymal (e.g. spindle, chondroid, osteoid) components. The established clonality of the different components, favours an evolution model encompassing either a multipotent progenitor, or a linear metaplastic conversion. Our study defines the micro-methylome and a spatial transcriptomic profile in MpBC, and identifies potential drivers associated with tumor heterogeneity that supports the conversion model of metaplasia and warrants further functional analysis. This submission includes only methylation arrays. Illumina Human Methylation EPIC BeadChip used for FFPE-origin DNA.