RNA-Sequencing Reveals Two Subgroups of Eccrine Porocarcinomas and Poromas

Area of Science:

• Oncology
• Dermatology
• Molecular Biology

Background:

• Eccrine porocarcinoma (EPC) is a rare malignant skin tumor that is poorly understood at the molecular level.
• Distinguishing malignant EPC from benign eccrine poroma (EP) based on molecular differences remains challenging despite known transcriptomic changes and fusions.

Purpose of the Study:

• To investigate the transcriptomic differences between EPC and EP.
• To identify molecular subgroups within these tumors and their potential link to gene fusions and signaling pathways.

Main Methods:

• RNA sequencing was performed on formalin-fixed, paraffin-embedded (FFPE) samples of 13 EPCs and 49 EPs.
• Histopathological features were assessed, and fusion genes were evaluated using NUT and YAP1 immunohistochemistry.

Main Results:

• EPC and EP samples clustered into two main transcriptomic groups based on differential expression of skin metabolism genes.
• The metabolism-low group included a subgroup enriched for Hedgehog pathway genes and samples with the YAP1-NUTM1 fusion.
• The metabolism-high group showed increased expression of genes related to immune processes, mesothelin, and Ras-MAPK signaling.

Conclusions:

• Transcriptomic subgroups exist in EPC and EP, partly associated with specific gene fusions.
• Further research into these disrupted signaling pathways is crucial for developing targeted therapies for rare eccrine gland tumors.