Spatial transcriptomic profiling of a rare case of rhabdoid carcinoma of the pancreas

Undifferentiated carcinoma of the pancreas with rhabdoid features is a rare and lethal variant, comprising less than one percent of all pancreatic cancer cases. Here we present a single patient case with in-depth molecular characterization, including whole exome DNA sequencing and GeoMx/CosMx spatial transcriptome profiling. DNA mutation analyses revealed a novel mutational profile in this case indicating wild-type KRAS and intact SMARCB1/INI1 alongside loss-of-function mutations in TP53, KMT2C, and KMT2D, and a Class II BRAF mutation. Spatial RNA analyses of tumor sections and adjacent pancreas revealed transcriptionally distinct cell types within the tumor and adjacent tissues. The unique transcriptomic features and mutational profile of this case highlight the heterogeneity of pancreatic cancers, even within rare variants, underscoring the need for early genomic profiling to identify actionable mutations such as BRAF that may respond to targeted therapies.