Single-cell exploration of gene expression and genotypes

Desmoid tumors comprise neoplastic and non-neoplastic cells, but how their cellular composition and interactions influence clinical behavior remains unclear. We are applying integrated single-nucleus and single-cell RNA sequencing with targeted genotyping of CTNNB1 and APC mutations to resolve tumor identity at single-cell resolution. Using biobanked desmoid tumor specimens, we are characterizing transcriptional profiles of genetically defined tumor and non-tumor cells. By linking these molecular profiles to clinical trajectories, we aim to identify gene expression programs associated with spontaneous regression and tumor-specific biology. Understanding these programs may reveal mechanisms that can be leveraged to induce regression in aggressive cases, and help identify patients who could be spared unnecessary or intensive therapy.