Spatially Resolved Ex Vivo Drug Response Profiling in SMARCB1-Deficient Sinonasal Carcinoma

ABSTRACT: SMARCB1-deficient sinonasal carcinoma (SDSC) is a rare, highly aggressive malignancy with limited therapeutic options and no established preclinical models. Here, single-nucleus RNA sequencing (snRNAseq), spatial transcriptomics, and ex vivo patient-derived tissue slice culture (TSC) were combined to resolve intratumoral heterogeneity, niche organization, and treatment vulnerabilities in an index SDSC. snRNAseq identified three malignant subpopulations, including two specialized states marked by ALDH1A1 and NTN4. Spatial profiling mapped these states to distinct niches. The ALDH1A1+ compartment localized to a basal-associated niche with intermingled p63-positive basal cells adjacent to stroma, showed reduced proliferative activity, and displayed stem-like transcriptional features. Ex vivo

SUBMITTER: Philipp Jurmeister 

PROVIDER: S-SCDT-10_1038-S44321-026-00437-1 | biostudies-other |

REPOSITORIES: biostudies-other