Ultra-Violet (UV) radiation from sunlight is the main carcinogen driving keratinocyte cancers of the skin. The accumulation of UV-induced mutations on sun-exposed areas leads to field cancerisation. Knowing the regenerative property of the skin, we investigated if epidermal ablation removes mutations on the epidermis and allows less mutated cells from the deeper part of the skin to repopulate the ablated surface. Patients with history of multiple epidermal cancers were subjected to epidermal ablation on their forearms with three different depths of laser (600nm, 400nm and fractional laser). Deep targeted DNA sequencing of 152 cancer related genes had revealed the mutation burdens on ablated and non-ablated epidermis. There were 12.9 mutations per Megabase (Muts/Mb) found in non-ablated control epidermis compared to 2.55 Muts/Mb in 600nm, 4.45 Muts/Mb in 400nm and 3.58 Muts/Mb in fractional laser ablated and regenerated epidermis (n=7). To evaluate the efficacy of epidermal ablation on keratinocyte cancers formation, we utilised a UVB inducible Basal Cell Carcinomas (BCC) murine model (K14Cre/ER::Ptch1lox/+ ). These mice were subjected to 10 weeks of UVB radiation. Half of the dorsal epidermis was ablated. before an additional 10 weeks of UVB radiation was administrated. Wholemount staining of a BCC biomarker, Keratin-17 (K17), revealed a significant reduction in the number of K17 patches in the ablated area (0.35 patches/mm2 ± 0.04 compared to 0.07 patches/mm2 ± 0.03) suggesting epidermal ablation can be used to reduce BCC occurrence. Deep targeted sequecning of the epidermis from the ablated and non-ablated area has revealed that there was 15-fold fewer mutations in the ablated area (18.65 mutations/Mb to 1.19 mutations/Mb). Overall, our findings propose a potential treatment to prevent accmulation of mutatoins in the skin. This study may also pave the way to a larger clinical trial of epidermal ablation as an adjuvant therapy for high-risk keratinocyte cancer patients.

ESDR246 - Epidermal ablation reduces keratinocyte cancer occurrence by reducing skin mutation burden caused by chronic ultraviolet radiation

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING