Is Rare Genetic Disorder Linked to Development of Squamous Cell Skin Cancer?
Posted: Monday, December 10, 2018
Patients a rare genetic disorder (recessive dystrophic epidermolysis bullosa [RDEB]) often develop squamous cell carcinoma of the skin, with a dismal 5-year survival rate. Andrew P. South, PhD, of Thomas Jefferson University, Philadelphia, and an international team of researchers sequenced the exomes of RDEB skin tumors and found that a group of enzymes, called apolipoprotein B editing complex (APOBEC), accounted for 42% of mutations in RDEB skin tumors. These results were published in Science Translational Medicine.
“Our findings reveal a cause for cancers arising at sites of persistent inflammation and identify potential therapeutic avenues to treat RDEB [cutaneous squamous cell carcinomas],” the investigators commented.
In patients with RDEB, APOBEC expression increasesd in response to the threat of infection, to the point that although the ultraviolet-induced driver mutation burden in these patients was 30%, endogenous processes increased this burden by 222%.
These mechanisms generated more than twice as many mutations in an RDEB squamous cell carcinoma than in an average human papillomavirus–negative, tobacco signature–negative head and neck squamous cell carcinoma but at less than half the average age.
The researchers sequenced 27 independent squamous cell carcinomas isolated from 26 patients with RDEB and compared them with data from 38 ultraviolet-induced squamous cell carcinomas and 279 head and neck squamous cell carcinoma tumors. A total of 38% of RDEB squamous cell carcinoma mutations were induced from ultraviolet exposure, compared with 78% of ultraviolet-induced squamous cell carcinomas.
Although APOBEC signatures did not correlate with age, patients with RDEB squamous cell carcinoma acquired 7.4 times more APOBEC mutations per year than patients with ultraviolet-induced squamous cell carcinoma and 8.3 times more often than patients with head and neck squamous cell carcinoma.
