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.