Whole exome-sequencing of vitiligo lesions indicate lower burden of somatic variations: implications in risk for non-melanoma skin cancers

Genetic depigmentary conditions such as albinism with complete loss of epidermal pigmentation pose a higher risk for cutaneous malignancies ( Lekalakala et al., 2015 ). 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 vitiligo subjects indicated a decreased risk for both melanoma and non-melanoma 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 a similar protection from non-melanoma skin cancer is perplexing. Therefore, these observations need to be substantiated with evidence at the tissue level. Recent advancements in genomics enables to map the somatic variations which would act as molecular correlate for cancer. In normal, seemingly healthy skin deep-sequencing of selected panel of cancer associated genes suggests pervasive positive selection of somatic variations that provides valuable insights into the origin of mutations and map their progression to skin cancers ( Martincorena et al., 2015 ; Zheng et al., 2021 )