Study Suggests Psoriasis Not Caused by Somatic Mutations in Skin

New research from the Wellcome Sanger Institute and collaborators suggests that psoriasis, a chronic skin condition, is not triggered or propagated by spontaneous genetic mutations within the skin. The study, published in Nature Genetics, sequenced skin samples from 111 individuals with psoriasis and found that mutated genes in psoriatic patches were also present in unaffected skin tissue of the same individuals.

Psoriasis is a widespread inflammatory immune-mediated disease that results in flaky or sore patches of skin. The exact cause of this condition, affecting an estimated 125 million people worldwide, remains unknown. This study focused on investigating whether somatic mutations, which accumulate in all cells over time due to replication errors, chemicals, or environmental factors, played a role in the development or progression of psoriasis.

Somatic mutations that offer a competitive advantage to a cell are known as driver mutations, potentially leading to uncontrolled growth and spread. While prior research had identified such mutations in diseases like inflammatory bowel disease, this study sought to determine if a similar mechanism was at play in psoriasis.

The research team collected skin samples from 111 psoriasis patients, both from affected patches and healthy skin areas. They analyzed 1,182 samples using whole genome or exome sequencing and discovered minimal differences in mutation types between healthy and psoriasis-afflicted skin. Furthermore, there were no functional disparities between psoriasis and non-psoriasis tissue, suggesting that somatic mutations in the skin are not linked to psoriasis.

Although the team identified four new driver mutations present in both psoriatic and non-psoriatic skin, they also found a mutational signature associated with psoralens, a compound sometimes used to treat psoriasis. Interestingly, these mutations were observed in patients who had and had not been prescribed psoralens, suggesting potential environmental factors at play.

Dr. Carl Anderson, the senior author of the study, emphasized that while the research did not identify specific genes with somatic mutations increasing susceptibility to psoriasis, it did quantify the mutational effects of psoralens on the skin, potentially aiding future research. Additionally, the study confirmed that the development of skin cells from stem cells remains unchanged in the presence of psoriasis. This discovery may lead to improved treatments for the millions of people affected by psoriasis worldwide.