Could germline variants in Hedgehog signaling pathway genes impact on melanoma predisposition?

Background: Germline variants in the Hedgehog signaling (SHH) pathway (PTCH1, PTCH2 and SUFU genes) predispose to Nevoid Basal-Cell Carcinoma Syndrome (NBCCS)/Gorlin Syndrome (GS) with high penetrance and variable expressivity. NBCCS/GS is a rare autosomal dominant disease characterized by a wide range of abnormalities and tumor predisposition, mainly multiple basal cell carcinomas (BCCs), medulloblastoma, cardiac and gonadal tumors [1]. It has also been reported that patients with basal cell carcinoma had a significantly higher incidence of melanoma than patients without basal cell carcinoma.