Psoriasis -; A chronic skin condition -; It is not caused or spread by spontaneous genetic mutations in the skin, new research suggests.
The team at the Wellcome Sanger Institute and colleagues sequenced skin samples from 111 people with psoriasis. They found no mutated genes in the psoriatic patches that were also mutated in the person’s intact skin tissue.
The study, published today (October 26). Nature geneticssuggesting that unlike other inflammatory diseases, such as inflammatory bowel disease or chronic liver disease, somatic mutations were not responsible for the initiation or progression of psoriasis.
Confirming that psoriasis is not caused by a somatic mutation enables researchers to continue exploring other avenues.
Over time, all the cells in our body will accumulate mutations, known as somatic mutations. They can arise from replication errors, chemicals or environmental factors. While some of these mutations can lead to cancer, many are harmless. When a mutation gives a cell an advantage over its neighbors, it is known as a driver mutation, and it allows the mutated cells to grow and spread.
Recently, research has begun to explore the possibility of driver mutations causing non-cancerous diseases by affecting tissue function or the spread of disease through the body.
In previous work by scientists at the Wellcome Sanger Institute, these mutations have been shown to affect diseases such as inflammatory bowel disease. In this new study, researchers and collaborators at the Wellcome Sanger Institute explored whether this is true for psoriasis.
Psoriasis is a chronic inflammatory immune-mediated disease that causes patches of skin that become flaky or sore. The current cause of the condition is unknown and it is estimated that 125 million people worldwide -; 2 to 3 percent of the total population -; Have psoriasis
The team took skin samples from the forearms of 111 people with psoriasis, psoriasis patches, and healthy skin. They used laser capture microdissection to isolate 1,182 samples, which were then analyzed by whole genome or exome sequencing.
They found minimal differences in the types of mutations seen in psoriasis patches versus healthy skin, and a slight increase in the number of mutations. In addition, no functional differences were observed between psoriasis and non-psoriasis tissue, suggesting that the condition is not associated with a specific somatic mutation in the skin.
The team identified four new driver mutations that gave skin cells an advantage over their neighbors, all found in psoriasis patches and other skin tissues. They also found a mutational signature associated with the use of psoralens, a compound that is sometimes used as part of the treatment of psoriasis flare-ups. However, these mutations were found in patients with whom they were prescribed psoralens, suggesting that they may have come from environmental exposure.
Dr Sigurjí Olafsson, first author, formerly at the Wellcome Sanger Institute, now at Decode Genetics in Iceland, said: “Studying somatic mutations in non-cancerous conditions has only become possible thanks to technological advances. Genetic analysis of non-cancerous diseases can help “identify new driver mutations, as we describe This adds to our growing collective knowledge of the impact of mutations in cancer and other diseases, as well as showing that specific treatments can influence the mutational landscape of a tissue.”
Psoriasis is a condition that affects millions of people around the world, affecting their quality of life, and little is known about why it occurs and how we can treat it. Although our study did not find a gene in which somatic mutations increase susceptibility to psoriasis, we were able to quantify the mutational consequences of psoralens exposure in the skin, defining a mutational signature that may aid future research. We also found that the way skin cells develop from stem cells is, reassuringly, unchanged by psoriasis.”
Dr. Karl Anderson, senior author of the Wellcome Sanger Institute
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Journal Reference:
Olafson, S., etc. (2023). Effects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin. Nature genetics. doi.org/10.1038/s41588-023-01545-1.