The genomic and spatial transcriptomic landscape of seborrheic keratoses.

Seborrheic keratosis is a common benign skin tumor that affects most individuals, particularly later in life. Despite its high prevalence, the underlying biology of seborrheic keratosis remains poorly understood. In this study, we performed whole-exome sequencing and spatial transcriptomics on a cohort of seborrheic keratosis and solar lentigo lesions to gain insight into their molecular landscape. Our results reveal a high mutational burden driven by solar UV damage, with recurrent somatic variants observed in genes such as FGFR3, NOTCH1, and TP53. Spatial transcriptomic analysis uncovered a complex tissue architecture with significant heterogeneity across lesion subtypes. Furthermore, differential gene expression analysis highlighted the dysregulation of the Wnt signaling pathway as a key feature in the pathogenesis of these lesions. Together, our findings provide insights into the molecular mechanisms driving seborrheic keratosis and solar lentigo, with implications for understanding their development and progression.