Cancer-related mutations can be found in around a quarter of skin cells belonging to healthy individuals. This is according to a new study published in the journal Science.
By performing ultra-deep genetic sequencing on 234 skin biopsies from cancer-free individuals, researchers from the Wellcome Trust Sanger Institute in the UK uncovered more than 100 cancer-associated mutations in every square centimeter of skin.
First study author Dr. Iñigo Martincorena and colleagues found that these mutations showed patterns linked to a non-melanoma skin cancer known as squamous cell carcinoma (SCC).
SCC is the second most common form of skin cancer in the US, affecting around 700,000 Americans annually. SCC is primarily caused by exposure to ultraviolet (UV) radiation from the sun over the course of a lifetime.
The researchers explain that cells with the mutations they identified had merged into clusters, known as “clones.” These clones had grown to become twice the normal size, although none of them had become cancerous, and Dr. Martincorena says it is unlikely any of them would have developed into skin cancer.
However, the team explains that these mutations are the first in a series of steps that can lead to the development of cancer.
“These first cancer-associated mutations give cells a boost compared to their normal neighbors. They have a burst of growth that increases the pool of cells waiting for the next mutation to push them even further,” explains study co-author Dr. Peter Campbell.
“We can even see some cells in normal skin that have taken two or three such steps toward cancer,” he adds. “How many of these steps are needed to become fully cancerous? Maybe five, maybe 10, we don’t know yet.”
The team reached their findings by analyzing the skin samples of four patients aged 55-73 who were having routine surgery to remove excess eyelid skin that was impairing their vision.
Overall, the researchers identified 3,760 mutations, finding over 100 SCC-related mutations in each square centimeter of skin.
The mutations, the team says, had accumulated over the course of each patient’s lifetime as their eyelids had been exposed to the sun. They estimate that each sun-exposed skin cell acquired a new mutation in its genome for almost each day of life.
The researchers explain their findings further in the video below:
While the researchers expected to find some cancer-related mutations in the biopsies, Dr. Martincorena told Medical News Today that they were surprised just how many they found.
“In retrospect,” he added, “the results may not be so surprising. For non-melanoma skin cancer to be relatively common in the population we may have expected many cells in healthy individuals to be part of the way to malignant transformation.”
These findings tell us a lot about how skin cancer develops, according to the team.
“We have learned that most of the genes known to be involved in non-melanoma skin cancer are already frequently mutated in normal skin,” Dr. Martincorena told MNT. “Yet, while these mutations are common in our skin, the chances of a single skin cell having all of the handful of mutations required to develop into a cancer are still low enough to explain why we don’t all get cancer.”
In addition, the researchers say their study highlights the importance of protecting our skin against the sun; greater sun exposure can lead to a greater number of mutations, raising our risk of skin cancer.
Study co-author Dr. Phil Jones adds:
“These kinds of mutations accumulate over time – whenever our skin is exposed to sunlight, we are at risk of adding to them.
Throughout our lives we need to protect our skin by using sun-block lotions, staying away from midday sun and covering exposed skin wherever possible. These precautions are important at any stage of life but particularly in children, who are busy growing new skin, and older people, who have already built up an array of mutations.”
The team says their findings also shed light on the origins of cancer and emphasize the value of analyzing normal tissue to find out more about how different types of cancer develop – something Dr. Martincorena told us they plan to do.
“Similar studies on other tissues and in a wider range of individuals and conditions would be fundamental to better understand the origin of different cancers, and to the future use of genetic data in cancer diagnosis and therapy,” he added.
In line with Skin Cancer Awareness Month this May, a recent Spotlight feature from MNT investigated the best ways to protect children against the sun.