Comparative Molecular Profiling of Basal Cell Carcinomas in Sun-Exposed and Anogenital Regions

Basal cell carcinoma (BCC) is the most common skin malignancy and is strongly associated with ultraviolet (UV) radiation. However, BCC arising in sun-protected areas such as the anogenital region remains poorly characterized. To compare the molecular profiles of anogenital BCC with those of BCC arising in sun-exposed skin, a retrospective analysis was performed on BCC cases identified between 2017 and 2025. Formalin-fixed, paraffin-embedded tissue samples were analyzed using a targeted next-generation sequencing panel (Oncomine Precision Assay GX). Clinicopathologic features and mutational profiles were compared. Nine anogenital BCC cases and 23 sun-exposed BCC cases were included. Mutations were identified in 14 of 23 (60.8%) sun-exposed cases, most commonly involving TP53, with additional alterations in SMO, FGFR3, ERBB2, RET, ERBB4, and PDGFRA. In contrast, no mutations were detected in the anogenital BCC group. Despite histologic similarity, anogenital BCC demonstrates a distinct molecular profile, suggesting an alternative pathogenesis. Further genomic studies are warranted.