It is well known that prolonged exposure to the sun's ultraviolet rays can cause DNA mutations that lead to skin cancer. Now new research suggests that inflammation from chronic skin injury can cause mutations that cause cancer with the help of a very special mechanism.
The researchers, led by scientists of the University of California University in San Francisco and Thomas Jefferson in Philadelphia, in cooperation with Nantomics LLC, located in Santa Cruz, said that a better understanding of this previously unseen method of forming tumors may lead to a new class of treatment for different types of cancer.
"We first describe the mechanism that incites to cancer, cause tissue damage," - said senior author Andrew South, Ph.D., assistant professor of dermatology and skin biology at Jefferson.
Previous studies of patients with head and neck cancer have suggested a link between inflammation and cancer tissues, but the specific mechanism of this relationship remains elusive.
In a new study, published August 22, 2018, in dermatology and genetics Science Translational Medicine, South and UCSF Health Raymond Cho, MD, Ph.D., first author of the study, the children studied cells with a rare skin disorder called recessive dystrophic epidermolysis BLM (RDEB). Patients with RDEB, sometimes are called "butterfly children" because their extreme fragility of the skin reminiscent of butterfly wings, lacking the connection protein collagen, which makes them prone to skin blistering and scarring at the slightest touch. In addition to severe pain and disfigurement potential patients also often develop aggressive squamous cancers at an early stage in life are often damaged areas.
«RDEB - terribly painful condition, but the cancer - this is what causes premature death in these patients," - said Cho, who is an assistant professor of dermatology at UCSF and a member of the Comprehensive Cancer Center, UCSF Helen Diller. "The reason that these patients develop cancer, is not entirely clear, but we realized that it must be directly related to chronic tissue damage, because the fragility of the skin is the basis of all of this disease."
Since RDEB rare - about five cases occur in every ten million born in the United States. You must collect a consortium of researchers from around the world to collect a sufficient number of tissue samples from children with the disease for the new samples including cancer, inflammation, and normal tissues. Rather than focus on a few genes associated with cancer, the researchers sequenced the entire protein-coding portion of the genome in these samples, which allowed them to detect subtle patterns of DNA mutations through gene in inflamed and cancerous tissue, which were distinctly different from the types of mutational signatures caused by UV radiation.
Researchers have shown that this pattern is caused by the mutation of a protein called APOBEC, which normally plays a role in adding to the diversity of cellular proteins and is considered to be protected against viruses. Patients with RDEB APOBEC becomes excessively active due to chronic inflammation of tissues, causing it to be administered via gene mutations, some of which ultimately lead to cancer.
Using a computational approach developed in the laboratory in the UCSF Cho, the researchers ruled out problems with the repair of DNA, which is a common driver for elevated levels of mutations in many cancers. Samples mutational density throughout the genome RDEB tissue samples showed that the normal DNA repair mechanisms are functioning properly, suggesting that mutations causing cancer, observed in patients with RDEB, were the result of inflammation, and dysfunctional APOBEC.
According to Cho, the concept that inflammation and cancer, one way or another, are connected, as in the medical world, and in the general public, according to Cho, he hopes that the new findings will help further studies of these relationships - in skin cancers, cancers of the neck and head and other conditions - more concrete.
"In many ways, cancer is like wounds that never heal," - said Cho. "Here we show a new mechanism for how chronic inflammation of the tissue damage can actually lead to cancer. This can provide the medical community with new opportunities for the development of preventive measures against cancer caused by inflammation, as we successfully cope with cancer caused by UV radiation. "