We have been long conceived that cancer cells are formed from developing oncogenic mutations during proliferation. On the other hand, it is very natural to think that normal tissue cells should have no or maybe very few (just to make it not too absolute) mutations. However, the latest Science paper by Martincorena et al. suggests that normal skin tissues do carry oncogenic mutations, in an amount that may be higher than you thought.
The group of scientists collected 234 biopsies of normal eyelid skin tissues from 4 individuals and sequenced 74 known cancer genes in them. What they've found is that the mutation rate of these genes in the sequenced skin tissues is actually as high as in many type of cancer tissues! It is comparable to the mutation rates of breast cancer and is only a factor of 10 less than that in a type of skin carcinoma!
How do healthy people, including us, have so many mutations in normal skin tissues? The answer is: sunlight. The study looked into specific changes in DNA of the mutated genes and found that they're common changes made by UV light, one of the major skin tumorgenic sources. Expansion of single mutated cells gives rise to the mutation pools. (Probably one more reason for us to apply sunscrean and avoid too much sunbathing indulgence...)
Why isn't everyone getting skin cancer if our eyelids all have so many mutations? Because as oncogenic mutations, they are not sufficient to transform "normal cells" to "cancer cells". The prevalent theory of cancer evolution in the cancer research field points that one mutation is not enough to drive the formation of a cancer cell and its expansion to form tumor. Accumulated (normally more than two) driver mutations really start tumor evolution (shown in the picture from Martincorena et al). However, Martincorena et al did show in the paper that cells with mutations in certain cancer genes gave them selection advantage during proliferation.
Cancer is indeed a complicated evolving process that is hard to control. The millions of cells that form our body go through proliferation everyday, bringing us with potentially high chances of genetic mutations. On the other hand, our body also has a powerful system (high-fidelity DNA repair, immune system) to protect us from getting cancer.
One interesting point is that for many of the immunotherapies that target mutated genes in cancer cells, they're also likely to kill some normal tissues which carry the same genetic mutations.
References:
The group of scientists collected 234 biopsies of normal eyelid skin tissues from 4 individuals and sequenced 74 known cancer genes in them. What they've found is that the mutation rate of these genes in the sequenced skin tissues is actually as high as in many type of cancer tissues! It is comparable to the mutation rates of breast cancer and is only a factor of 10 less than that in a type of skin carcinoma!
How do healthy people, including us, have so many mutations in normal skin tissues? The answer is: sunlight. The study looked into specific changes in DNA of the mutated genes and found that they're common changes made by UV light, one of the major skin tumorgenic sources. Expansion of single mutated cells gives rise to the mutation pools. (Probably one more reason for us to apply sunscrean and avoid too much sunbathing indulgence...)
Why isn't everyone getting skin cancer if our eyelids all have so many mutations? Because as oncogenic mutations, they are not sufficient to transform "normal cells" to "cancer cells". The prevalent theory of cancer evolution in the cancer research field points that one mutation is not enough to drive the formation of a cancer cell and its expansion to form tumor. Accumulated (normally more than two) driver mutations really start tumor evolution (shown in the picture from Martincorena et al). However, Martincorena et al did show in the paper that cells with mutations in certain cancer genes gave them selection advantage during proliferation.
Cancer is indeed a complicated evolving process that is hard to control. The millions of cells that form our body go through proliferation everyday, bringing us with potentially high chances of genetic mutations. On the other hand, our body also has a powerful system (high-fidelity DNA repair, immune system) to protect us from getting cancer.
One interesting point is that for many of the immunotherapies that target mutated genes in cancer cells, they're also likely to kill some normal tissues which carry the same genetic mutations.
References:
Martincorena et al. Science 22 May 2015: 880-886
Douglas E. Brash Science 22
May 2015: 867-868.
Comments
Post a Comment