Whole-Exome Sequencing of Vitiligo Lesions Indicates Lower Burden of Somatic Variations: Implications in Risk for Nonmelanoma Skin Cancers

Abstract

Genetic depigmentary conditions such as albinism with complete loss of epidermal pigmentation pose a higher risk for cutaneous malignancies (Lekalakala et al., 2015; Kromberg et al., 1989). By analogy, clinical management for photoprotection of the acquired depigmented skin in vitiligo is of serious concern. It is believed that vitiligo would pose a similar, elevated risk. Systematic evaluation of a large cohort of subjects with vitiligo indicated a decreased risk for both melanoma and nonmelanoma skin cancers (Hexsel et al., 2009; Kim et al., 2020; Paradisi et al., 2014; Rodrigues, 2017; Schallreuter et al., 2002; Teulings et al., 2013; Weng et al., 2021). Extrapolating from demographic studies, it is tempting to speculate that vitiligo could negatively influence either initiation or progression of cutaneous malignancies (Rodrigues, 2017). Given the autoimmune etiology that targets melanocyte destruction, protection against melanoma could be rationalized; however, similar protection from nonmelanoma skin cancer is perplexing. Therefore, these observations need to be substantiated with evidence at the tissue level. Recent advancements in genomics enable the mapping of the somatic variations that would act as a molecular correlate for cancer. In normal, seemingly healthy skin, deep sequencing of a selected panel of cancer-associated genes suggests a pervasive positive selection of somatic variations that provides valuable insights into the origin of somatic variations and map their progression to skin cancers