Researchers have shown that somatic USP8 gene mutations are a common cause of pediatric Cushing disease (CD), according to a study recently published in The Journal of Clinical Endocrinology & Metabolism.
The team, led by Constantine A. Stratakis, MD, of the National Institutes of Health in Bethesda, Md., point out that this mutation has been identified as the culprit in patients with CD, but the frequency of these mutations hasn’t been studied as extensively in the pediatric population. So the researchers analyzed DNA samples from 42 pediatric patients with CD, and compared the data between patients with and without somatic USP8 mutations.
Five different mutations were identified in one-third of these patients, which is in line with the reported frequency in the adult population with CD. The researchers also found that this mutation is linked to higher rates of recurrence of the tumor.
The authors write that they acknowledge the small sample size as a limitation to this study, but pediatric CD is a rare disease, and this cohort is the largest of its kind so far. They also point out that the patients in the cohort may have had more aggressive tumors to begin with, since they had to select patients with both blood and tissue samples, “and the detection of the USP8 defect in them may be a coincidence rather than causative.” They write that this study is part of a larger one aimed at defining genetic cause of CD in children and adults, and that “additional studies are needed to define the effect of a USP8 defect in the biologic behavior of an ACTH-producing tumor in both children and adults.”