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Wellcome Sanger Institute scientists rule out one potential cause of psoriasis





It affects an estimated 125 million people around the world, yet we know very little about what causes it and how to treat it.

Now scientists at the Wellcome Sanger Institute and their collaborators have ruled out the idea that the chronic skin condition psoriasis is caused or spread by spontaneous genetic mutations in the skin.

Psoriasis on an elbow
Psoriasis on an elbow

After sequencing skin samples from 111 people with psoriasis, they did not find any mutated genes in the psoriatic patches that were not also mutated in the individual’s unaffected skin tissue.

The finding that somatic mutations are not responsible for the start or spread of psoriasis separates it from other inflammatory diseases, such as inflammatory bowel disease or chronic liver disease.

And it means researchers can explore other avenues for the causes of the immune-mediated disease, which affects two to three per cent of the global population and causes patches of skin to become flaky or sore.

Somatic mutations are accumulated in all cells in our bodies over time and can arise from replication errors, chemicals or environmental factors. Some of these mutations can lead to cancer, but many are harmless.

If a mutation gives the cell an advantage over its neighbours, it is known as a driver mutation, and allows mutated cells to grow and spread.

Recent research has begun exploring the idea that driver mutations could cause non-cancerous diseases by impacting the function of the tissue or influencing the spread of disease.

Sanger Institute scientists have previously shown such mutations have an impact on inflammatory bowel disease.

To see if the same was true for psoriasis, the researchers took skin samples from the forearms of 111 people with psoriasis, including from patches with and without psoriasis, then used laser capture microdissection to isolate 1,182 samples for analysis by whole genome or exome sequencing.

They found minimal differences between the two types of samples and only a slight increase in the number of mutations. And there were no functional differences between the two types of tissue.

But they did find four new driver mutations that gave skin cells an advantage over their neighbours in both psoriasis patches and other skin tissue.

And they found a mutational signature linked to the use of psoralens, which is a compound sometimes used in the treatment of psoriasis flare-ups. These mutations, however, were found in both patients that had and had not been prescribed psoralens, which suggest it could have come from environmental exposure.

Dr Sigurgeir Olafsson, first author previously from the Wellcome Sanger Institute, now at deCODE genetics in Iceland, said: “Studying somatic mutations in non-cancerous conditions has only become possible recently thanks to technological advancements. Genetic analysis of non-cancerous diseases can help identify new driver mutations, such as those we describe. This adds to our growing collective knowledge about the impact of mutations on cancer and other diseases, as well as showing that certain treatments can influence the mutational landscape of a tissue.”

Dr Carl Anderson, senior author from the Wellcome Sanger Institute, added: “Psoriasis is a condition that affects millions of people around the world, impacting their quality of life, and very little is known about why it happens and how we can treat it. While our research did not find a gene where somatic mutations increase susceptibility to psoriasis, we were able to quantify the mutational consequences of psoralens exposure on the skin, defining a mutational signature that may help future research.We also found that the way in which skin cells develop from stem cells is, reassuringly, unaltered by psoriasis.”

The study was published in Nature Genetics.



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