A comprehensive study carried out by the Wellcome Sanger Institute, along with other collaborators, involved sequencing skin samples from 111 individuals suffering from psoriasis. What stood out was the absence of any altered genes in the affected psoriasis patches that weren’t already altered in the person's unaffected skin tissue. This information, now published in Nature Genetics, highlights a marked difference between psoriasis and other inflammatory ailments such as inflammatory bowel disease or chronic liver disease. The new findings emphasize that somatic mutations don't play a role in the onset or progression of psoriasis.
Somatic Mutations: A Background
With time, every cell in our system will undergo somatic mutations, changes that can emerge due to replication errors, chemicals, or external environmental elements. Some of these mutations can instigate cancer, but many remain benign. A particular type of mutation, known as a driver mutation, empowers a cell with a distinct advantage over its counterparts, paving the way for these altered cells to flourish.
Recent scientific pursuits have been investigating the role of these driver mutations in triggering non-cancerous ailments, especially those that may influence the tissue's functioning or the disease's movement throughout the body.
For context, prior studies by the scientists at the Wellcome Sanger Institute demonstrated the influence of these mutations on conditions like inflammatory bowel disease. The question at hand was whether a similar pattern existed for psoriasis.
Delving Deeper into Psoriasis
Affecting approximately 125 million individuals globally—roughly 2 to 3 percent of the entire population—psoriasis is a persisting inflammatory condition where the immune system plays a significant role1. This disease manifests as patches on the skin that turn flaky or painful. The primary cause remains a mystery.
To gain clarity, the researchers extracted skin samples from 111 psoriasis-affected individuals. These samples, sourced from both healthy skin and psoriasis patches, underwent detailed examination. Utilizing laser capture microdissection, they managed to isolate 1,182 samples. These samples then went through whole genome or exome sequencing.
What emerged was a negligible difference in mutation types between healthy skin and the affected psoriasis patches. There was only a minor uptick in the mutation count. Furthermore, the team couldn’t pinpoint any functional disparities between the two skin types, reinforcing the idea that psoriasis doesn't arise due to specific somatic mutations.
Interestingly, the team stumbled upon four new driver mutations, which were found equally in psoriasis patches and unaffected skin. They also identified a mutational signature associated with the use of psoralens, occasionally employed in treating psoriasis flare-ups. Yet, these mutations were detected both in patients who had and hadn't been treated with psoralens, hinting at a possible environmental source.
Dr. Sigurgeir Olafsson, previously from the Wellcome Sanger Institute, commented, “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.”
Lastly, Dr. Carl Anderson of the Wellcome Sanger Institute remarked, “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.”
References
- National Psoriasis Foundation. Available at https://www.psoriasis.org/psoriasis-...y%20consortium [Accessed October 2023]