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Menggunakan kulit yang sehat untuk mengidentifikasi asal-usul kanker : perubahan DNA Kanker terkait di 25 persen dari sel-sel kulit normal
Date:
May 21, 2015
Source:
Wellcome Trust Sanger Institute
Summary:
Kulit normal mengandung jumlah tinggi tak terduga dari mutasi terkait kanker , menurut sebuah penelitian . langkah pertama sel menuju menjadi kanker dan menunjukkan nilai yang menganalisis jaringan normal untuk mempelajari lebih lanjut tentang asal-usul penyakit ....read more
Using healthy skin to identify cancer’s
origins: Cancer-associated DNA changes in 25 per cent of normal skin cells
Date:
May 21, 2015
Source:
Wellcome Trust Sanger Institute
Summary:
Normal skin contains an unexpectedly high number of cancer-associated mutations,
according to a study. 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.
..........................
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.
Story Source:
The above story is based on materials provided by Wellcome
Trust Sanger Institute. Note: Materials may be edited for content
and length.
Journal Reference:
1.
Peter J. Campbell et al. High burden and pervasive positive
selection of somatic mutations in normal human skin. Science,
May 2015 DOI:10.1126/science.aaa6806