Insights From Mutational and Transcriptomic Profiles in Epithelial-myoepithelial Carcinoma

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland malignancy.
• HRAS mutations are frequently observed in EMC.
• Understanding EMC's molecular profile is key for diagnosis and treatment.

Purpose of the Study:

• To define the molecular and transcriptomic landscape of EMC.
• To explore EMC's relationship with other head and neck neoplasms, especially basal cell adenoma (BCA).
• To identify diagnostic markers for differentiating EMC and BCA.

Main Methods:

• Retrospective analysis of 14 EMC cases.
• Histology, immunohistochemistry, and whole-exome capture RNA sequencing.
• Comparative analysis with 54 RAS-mutated head and neck tumors.

Main Results:

• HRAS mutations (predominantly p.Gly61Arg) found in 57% of EMC.
• Identified additional mutations (PIK3CA, STAT5B, NOTCH1) and gene fusions (HMGA2::WIF1, FBXO32::PLAG1).
• EMC and BCA share transcriptomic similarities; EMC shows Ras-Raf-MAPK and PI3K-Akt pathway activation.

Conclusions:

• HRAS mutations are not exclusive to EMC and are found in benign BCA.
• Transcriptomic profiling reveals similarities between EMC and BCA.
• Integrated molecular analysis is essential for distinguishing EMC from other salivary gland tumors.