Distinct driver genes and the expression of Hedgehog defines morphoeic basal cell carcinoma

NK importance may be greater in mBCC and represents a novel therapeutic target. Aberrant Hedgehog (Hh) pathway signalling was shown to be more critical in mBCC than nodBCC on three molecular levels: mutational burden, transcriptome profile and protein expression. Surrounding mBCC stroma is abnormal, containing mutations in EPHA3, ATR, and GLI3.

Hh pathway over-expression is seen in the tumour and stroma of morphoeic tissue, but not nodular, with the stroma potentially contributing to the morphoeic’s aggressive nature and local recurrence risk. These findings have implications for clinical practice by highlighting novel therapeutic targets for mBCC and the potential need to remove surrounding stroma to prevent local recurrence.