GOOD SKIN CONTAINS MANY CANCER LINKED MUTATIONS
Normal
skin contains an unexpectedly high number of cancer-associated mutations,
according to a study published in Science.The findings illuminate the first steps cells take
towards becoming a cancer and demonstrate the value of analyzing normal tissue
to learn more about the origins of the disease
The study revealed
that each cell in normal facial skin carries many thousands of mutations,
mainly caused by exposure to sunlight. In fact, around 25 per cent of skin
cells in samples from people without cancer were found to carry at least one
cancer-associated mutation. Ultra-deep genetic sequencing was performed on 234
biopsies taken from four patients revealing 3,760 mutations, with more than 100
cancer-associated mutations per square centimetre of skin. Cells with these
mutations formed clusters of cells, known as clones, that had grown to be
around twice the size of normal clones, but none of them had become cancerous.
"With this
technology, we can now peer into the first steps a cell takes to become
cancerous," explains Dr Peter Campbell, a corresponding author from the
Wellcome Trust Sanger Institute. "These first cancer-associated mutations
give cells a boost compared to their normal neighbours. They have a burst of
growth that increases the pool of cells waiting for the next mutation to push
them even further. We can even see some cells in normal skin that have taken
two or three such steps towards cancer. How many of these steps are needed to
become fully cancerous? Maybe five, maybe 10, we don't know yet."
The mutations observed
showed the patterns associated with the most common and treatable form of skin
cancer linked to sun exposure, known as cutaneous squamous cell carcinoma,
rather than melanoma, a rarer and sometimes fatal form of skin cancer.
"The burden of
mutations observed is high but almost certainly none of these clones would have
developed into skin cancer," explains Dr Iñigo Martincorena, first author
from the Sanger Institute. "Because skin cancers are so common in the
population, it makes sense that individuals would carry a large number of
mutations. What we are seeing here are the hidden depths of the iceberg, not
just the relatively small number that break through the surface waters to
become cancer."
Skin samples used in
this study were taken from four people aged between 55 and 73 who were
undergoing routine surgery to remove excess eyelid skin that was obscuring
vision. The mutations had accumulated over each individual's lifetime as the
eyelids were exposed to sunshine. The researchers estimate that each
sun-exposed skin cell accumulated on average a new mutation in its genome for
nearly every day of life.
"These kinds of
mutations accumulate over time -- whenever our skin is exposed to sunlight, we
are at risk of adding to them," explains Dr Phil Jones, a corresponding
author from the Sanger Institute and the MRC Cancer Unit at the University of
Cambridge. "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."
Recent studies
analysing blood samples from people who do not have cancer had revealed a lower
burden of mutations, with only a small percentage of individuals carrying a
cancer-causing mutation in their blood cells. Owing to sun exposure, skin is
much more heavily mutated, with thousands of cancer-associated mutations
expected in any adult's skin.
The results
demonstrate the potential of using normal tissue to better understand the
origins of cancer. The Cancer Genomics group at the Sanger Institute will
continue this work with larger sample numbers and a broader range of tissues to
understand how healthy cells transition into cancerous cells.
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