RNA-Sequencing Reveals Two Subgroups of Eccrine Porocarcinomas and Poromas

Eccrine porocarcinoma (EPC), a rare malignant eccrine gland tumour, remains molecularly understudied. Transcriptomic studies of EPC and benign eccrine poroma (EP) have identified recurrent fusions and expression changes, but differences distinguishing malignant EPC from benign EP are unclear. RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) samples (13 EPCs and 49 EPs) from Helsinki Biobank and Finnish Clinical Biobank Tampere. RNA sequencing characterized transcriptomic profiles. Histopathological features were assessed on haematoxylin-eosin-stained sections, and fusion genes were evaluated by NUT and YAP1 immunohistochemistry. EPCs and EPs clustered into two transcriptomic groups regardless of tumour subtype, primarily distinguished by differential expression of genes involved in skin metabolism. The metabolism-high group showed higher expression of genes associated with immune-related processes, mesothelin, and Ras-MAPK signalling. The metabolism-low group contained a subgroup enriched for Hedgehog pathway-associated genes, such as GLI1, GLI2, HHIP, LRP2, and PTCH2. All samples with the YAP1-NUTM1 fusion pattern belonged to the metabolism-low group and showed elevated NUTM1 expression in the heatmap. RNA sequencing revealed transcriptomic subgroups in EPC/EP partly linked to fusions. The results underscore the necessity for further investigation into the disrupted signalling pathways, which may facilitate the development of targeted therapies.