Chronic Inflammation Can Trigger Cancers Via Newly Discovered Mechanism

It is well known that extended exposure to the sun’s UV rays can cause DNA mutations that lead to skin cancer. Now new research reveals that inflammation from chronic skin injury can trigger cancer-causing mutations as well by a totally distinct mechanism.

In a new study, published August 22, 2018, in Science Translational Medicine, Andrew South, PhD, an associate professor in the Department of Dermatology and Cutaneous Biology at Jefferson and UCSF Health dermatologist and geneticist Raymond Cho, MD, PhD, the study’s first author, studied the cells of children with a rare skin disorder called recessive dystrophic epidermolysis bullosa (RDEB). Patients with RDEB lack the connective protein collagen, which makes their skin prone to blistering and scarring at the slightest touch and they frequently develop aggressive squamous cell cancers early in life in frequently injured areas. 

The researchers sequenced the entire protein-coding part of the genome in samples from RDEB patients, which enabled them to detect subtle patterns of DNA mutation across the genome in inflamed and cancerous tissue that were clearly distinct from the types of mutational signatures caused by UV radiation.

The researchers showed that this pattern of mutation is caused by a protein called APOBEC, which normally plays a role in adding diversity to cellular proteins and is also thought to help defend against viruses. 

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A microscopic view of an invasive squamous cell cancer that stemmed from a rare skin disorder called recessive dystrophic epidermolysis bullosa (RDEB), or Butterfly Syndrome. Credit: Andrew South